What is Transthyretin Amyloid Cardiomyopathy?
Transthyretin amyloid cardiomyopathy (ATTR-CM), previously known as senile systemic amyloidosis (SSA), is a rare heart condition caused by the buildup of abnormal deposits of a protein called transthyretin (TTR) in the heart. TTR is mainly produced in the liver and transports thyroxine and retinol-binding protein. Mutations in the TTR gene or aging can cause TTR to fold abnormally and clump together to form amyloid fibrils that gradually damage organs and tissues. The heart is one of the main targets and amyloid deposits impair its functioning, leading to heart failure. The main symptoms include fatigue, shortness of breath, swelling in the legs and abdomen, and irregular heartbeat.
Diagnosing Transthyretin Amyloid Cardiomyopathy
Diagnosis begins with a physical exam and medical history to check for symptoms. Echocardiogram can show thickening of the heart walls due to amyloid deposits while magnetic resonance imaging (MRI) provides clues to amyloidosis. Blood tests look for elevated levels of troponin and NT-proBNP, markers of heart damage. Tissue biopsy with imaging techniques like technetium scintigraphy can confirm the amyloid deposits are made of abnormal TTR protein. Genetic testing helps differentiate between hereditary and wild-type Transthyretin Amyloid Cardiomyopathy Treatment based on mutations in the TTR gene. A heart biopsy examining a small sample of heart muscle under a microscope is the gold standard test and is needed for a definitive diagnosis.
Transthyretin Amyloid Cardiomyopathy Treatment Options
Currently available treatment aims to slow the progression of organ damage by ATTR amyloid deposits. For hereditary ATTR or mutant gene carriers, liver transplantation is done to remove the source of mutant TTR production but may not halt cardiac involvement. Medications specifically targeting TTR stabilization are the main treatment. Tafamidis binds and stabilizes normal and some mutated forms of TTR protein slowing its misfolding. Inotersen is an antisense oligonucleotide that inhibits TTR mRNA expression and protein production in the liver. Recently, patisiran and eplontersen were approved which are RNA interference therapeutic agents inhibiting TTR synthesis.
Heart failure drugs and devices to control symptoms are also used depending on severity of cardiac amyloidosis. Angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists may help but have limited efficacy. Device therapy involves implanting a biventricular pacemaker (CRT) or implantable cardioverter-defibrillator (ICD) to treat arrhythmias and stabilize heartbeat. Lastly, a heart transplant may be considered for carefully selected younger patients with end-stage heart failure from ATTR-CM. Promising new gene silencing therapies are under clinical trials.
Managing Complications of Transthyretin Amyloidosis
Given the systemic nature of the disease, managing complications in other organs like kidneys, peripheral nervous system, and gastrointestinal tract is also important. Kidney dysfunction may require dialysis while carpal tunnel syndrome or other neuropathies are handled through splinting, medication, or surgery. Gastrointestinal problems like malnutrition or malabsorption are addressed by maintaining a high-calorie diet and nutritional supplements. Nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided due to risk of kidney injury or worsening amyloid deposits. Vaccinations may have reduced effectiveness in people with advanced amyloidosis and related immunosuppression. Counseling can help cope with this progressive systemic disease.
Current Clinical Trials in Transthyretin Amyloidosis
With novel therapeutic approaches, ongoing clinical studies aim to improve cardiological outcomes and quality of life for ATTR-CM patients. Several gene silencing therapies are under phase 3 trials to determine long-term safety and effectiveness in reducing mortality and hospitalizations. Vutrisiran is a subcutaneous RNAi therapy while eplontersen is administered intravenously. Others in late-stage development are fitusiran an RNAi therapy and donor-derived hematopoietic cell transplantation approach. Phase 2 trials are evaluating combination therapies using tafamidis with patisiran or inotersen. Investigational drugs inhibiting amyloid fibril formation or inducing its clearance are also under early trials. With advances in diagnostic tools, targeted therapies and better understanding of disease mechanisms, management of ATTR amyloidosis continues to evolve.
This article provided an overview of Transthyretin Amyloid Cardiomyopathy Treatment or ATTR-CM including its causes, diagnosis, current treatment approaches and management of complications. It discussed medications specifically designed to target the underlying protein abnormality as well as device-based therapies and transplant options. Ongoing clinical research was highlighted to bring more effective and safer treatments for improving outcomes in patients with this progressive heart condition caused by abnormal transthyretin protein deposition in the heart muscles.
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Ravina Pandya, Content Writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. (https://www.linkedin.com/in/ravina-pandya-1a3984191)