What is wild-type transthyretin (ATTR) amyloidosis?

From the Guidelines

Wild type ATTR (ATTRwt) is a form of amyloidosis that requires early diagnosis and treatment to improve morbidity, mortality, and quality of life, and the most recent evidence suggests that a combination of cardiac imaging, nuclear scintigraphy, and sometimes tissue biopsy is necessary for diagnosis, with treatment focusing on managing heart failure symptoms and disease-modifying therapies like tafamidis (1). The condition typically affects older adults, particularly men over 65, causing progressive heart failure with symptoms like shortness of breath, fatigue, and peripheral edema.

• Diagnosis of ATTRwt requires a combination of:
  • Cardiac imaging (echocardiogram, cardiac MRI) to assess left ventricular wall thickness and diastolic dysfunction (1)
  • Nuclear scintigraphy (technetium pyrophosphate scan) to detect amyloid deposits in the heart (1)
  • Sometimes tissue biopsy to confirm the presence of amyloid deposits and determine the subtype of amyloidosis (1)
• Treatment of ATTRwt focuses on managing heart failure symptoms with diuretics like furosemide (20-80mg daily) and spironolactone (25-50mg daily), as well as disease-modifying therapies like tafamidis (Vyndaqel 61mg or Vyndamax 61mg once daily) (1)
• Other options for treatment include patisiran and inotersen, which reduce transthyretin production, and heart transplantation may be considered in select cases (1)
• Regular cardiology follow-up every 3-6 months is essential to monitor disease progression and adjust treatment (1)
• Unlike hereditary ATTR, wild type ATTR is not genetic and doesn't require family screening, but early diagnosis is crucial for optimal management and improved outcomes (1)

From the FDA Drug Label

VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. VYNDAQEL and VYNDAMAX are prescription medicines used to treat adults with cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems. The treatment of wild-type ATTR with tafamidis is indicated to reduce cardiovascular mortality and cardiovascular-related hospitalization in adults 2.

• The drug labels support the use of VYNDAQEL and VYNDAMAX for this indication.
• Tafamidis has been shown to have a significant treatment effect on functional capacity and health status in patients with wild-type ATTR 2.

From the Research

Wild Type ATTR

• Wild-type transthyretin (ATTRwt) amyloidosis is a progressive condition characterized by the deposition of wild-type transthyretin in the body, often affecting the heart and leading to cardiomyopathy 3.
• The clinical spectrum of wild-type ATTR amyloidosis includes cardiomyopathy, carpal tunnel syndrome, and other manifestations, with the phenotypes varying depending on the individual and the presence of other factors 3.
• Treatment options for wild-type ATTR amyloidosis include disease-modifying therapies such as tafamidis, which stabilizes the TTR tetramer and inhibits the formation of amyloid fibrils 4, 5, 6.
• Tafamidis has been shown to be effective in reducing mortality and cardiovascular-related hospitalizations in patients with wild-type ATTR cardiomyopathy, with benefits observed in both clinical and biomarker domains 7, 6.
• Monitoring of disease progression in patients with wild-type ATTR cardiomyopathy is crucial, with a multiparametric approach recommended, including clinical, biomarker, and imaging/ECG assessments 7.
• Other treatment options, such as diflunisal, have also been investigated, with studies suggesting its efficacy in stabilizing the TTR tetramer and reducing mortality risk in patients with ATTR cardiomyopathy 4.

Treatment Options

• Tafamidis is a TTR stabilizer that has been approved for the treatment of adults with transthyretin amyloid cardiomyopathy (ATTR-CM) 6.
• Diflunisal is a low-cost, off-label drug that has been shown to stabilize the TTR tetramer and reduce mortality risk in patients with ATTR cardiomyopathy 4, 5.
• Gene silencers, such as patisiran and inotersen, have also been approved for the treatment of ATTR amyloidosis, and work by reducing the production of TTR in the liver 5, 3.

Disease Progression

• Disease progression in wild-type ATTR cardiomyopathy can be monitored using a multiparametric approach, including clinical, biomarker, and imaging/ECG assessments 7.
• The frequency of disease progression markers, such as changes in cardiac magnetic resonance (CMR) tomography, can provide valuable insights into the effectiveness of treatment and the need for adjustments to the treatment plan 7.