by Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive heart disease caused by the buildup of abnormal deposits of a protein called transthyretin in the heart muscle. These deposits, called amyloid fibrils, weaken the heart muscle and affect how well the heart pumps blood through the body. Until recently, ATTR-CM has been challenging to diagnose and treat. However, advances in research have led to improved understanding, testing and management of this disease. This article provides an overview of the current state of ATTR-CM treatment.
Causes and Types of ATTR-CM
ATTR-CM is caused by mutations in the Transthyretin Amyloid Cardiomyopathy Treatment transthyretin (TTR) gene. TTR is a protein produced mainly in the liver and eye. Mutations in TTR cause it to take on abnormal amyloid fibril formations that gradually build up in tissues and organs such as the heart. There are two main types of ATTR-CM:
– Hereditary ATTR amyloidosis – Caused by inherited or genetic mutations in the TTR gene. Symptoms usually appear between ages 50-70.
– Wild-type ATTR amyloidosis – Not inherited or genetic, but rather associated with aging. Symptoms typically affect those over age 80.
Both forms ultimately lead to amyloid fibril deposits in the heart muscle, compromising its ability to pump blood effectively. Over time, this causes symptoms of heart failure and functional decline.
Diagnosis and Testing
Diagnosis of ATTR-CM involves a combination of tests to confirm amyloid deposits in tissues along with genetic testing to identify a TTR mutation if present. Tests may include:
– Echocardiogram and cardiac magnetic resonance imaging (MRI) to assess heart structure and function.
– Bone scintigraphy (bone scan) to detect abnormal radioactive tracer uptake suggestive of amyloidosis.
– Fat pad or abdominal fat aspiration biopsy examined under a microscope for amyloid fibrils.
– Blood tests such as troponin levels and NT-proBNP levels to check for heart damage.
– Genetic testing of blood sample to identify any pathogenic TTR gene mutations.
An experienced doctor can make the ATTR-CM diagnosis by correlating exam findings, test results and disease characteristics. Establishing a definite diagnosis is important for selecting the appropriate treatment approaches.
Treatment Approaches
Once diagnosed, treatment of ATTR-CM focuses on two main approaches:
- Organ transplantation: Liver transplantation is the standard treatment for hereditary ATTR amyloidosis as it eliminates production of mutated TTR protein by the liver. Combined heart-liver transplantation may be required for advanced cardiac involvement. However, transplantation is a major surgical procedure with risks that need to be balanced against potential benefits.
- Medication therapy: For those who cannot undergo transplantation, novel disease-modifying therapies targeting the underlying amyloid fibril deposits are becoming available. These include:
– Tafamidis: A TTR stabilizer drug that binds to and prevents abnormal conformational changes in TTR tetramers leading to amyloid formation. Approved to slow disease progression.
– Inotersen and Patisiran: RNA interference therapies that inhibit TTR gene expression and production. Approved for stabilizing neurologic dysfunction in hereditary ATTR amyloidosis. Benefits for cardiomyopathy still under study.
– Anti-amyloid antibodies: Experimental monoclonal antibody therapies designed to promote removal of existing amyloid deposits from tissues. Some early trial results show heart improvement.
– Small interfering RNAs (siRNAs): Another investigational approach using small snippets of genetic material to inhibit TTR mRNA translation into protein. Potential future role.
Medication management also focuses on optimizing diuretics, beta-blockers and angiotensin receptor blockers to ease symptoms of heart failure and stabilize cardiac function for as long as possible.
Prognosis
Without treatment, ATTR-CM has a poor long term prognosis with median survival of 2-3.5 years from symptom onset. Mortality results from progressive heart failure and arrhythmias. Liver transplantation significantly extends survival for hereditary forms. The newer disease-modifying therapies have shown potential to halt cardiac deterioration and improve quality of life based on initial clinical trial data. However, long term outcomes with these agents still need further study.
Advancing research into ATTR-CM promises more targeted treatment options that can dramatically change the disease trajectory and prognosis in the future. Areas of active investigation include improved amyloid-targeting drugs, gene-silencing strategies and stem cell therapies. As diagnostic capabilities grow with wider disease recognition, it is hoped that ATTR-CM may transform from a rapidly fatal illness to one with a more manageable long term course through timely diagnosis and optimized care.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
