Transthyretin amyloidosis (ATTR) remains an underdiagnosed and underrecognised disease despite several guidelines available that inform its diagnosis and care.1,2 ATTR, which can show up in different forms, and its symptoms are commonly misattributed to other conditions.3 Patients with ATTR need a timely diagnosis and specialised plan to slow disease progression and improve their quality of life.
What is transthyretin amyloidosis (ATTR)?
ATTR is a potentially fatal type of amyloidosis that is challenging to diagnose because its symptoms resemble other, more common conditions.4 The disease causes transthyretin (TTR) proteins to misfold and clump together in the form of fibrils.5-6
For people with ATTR, these fibrils build up in organs such as the heart, kidneys, peripheral nervous system and the brain, causing tissue damage.7 ATTR then causes complications, leading to cardiovascular, neurological and renal diseases such as heart failure and chronic kidney disease.8-10
ATTR has several phenotypes including ATTR-cardiomyopathy (CM), which impacts the heart, potentially leading to heart failure, ATTR-polyneuropathy (PN), which affects the peripheral nervous system including the brain, and mixed phenotype, where patients experience symptoms of both.8-9
ATTR and its phenotypes can be caused by genetics and aging
Patients may have either ATTR-CM or ATTRv-PN, or both cardiac and neurologic symptoms, diagnosed as mixed phenotype. ATTR-CM is most often related to aging, but ATTRv-PN can be passed down in families through genetics since it is usually hereditary.11,12 Estimates show about 300,000 to 500,000 people around the globe currently live with ATTR-CM and 10,000 to 40,000 have ATTRv-PN.12,13 Patients with these ATTR phenotypes typically experience a reduced quality of life with a high mortality rate.2,4,7,14
ATTR-CM is a systemic, progressive and ultimately fatal condition that can lead to heart failure within several years of onset.3 As amyloid fibrils build up in the heart’s main pumping chamber, the left ventricle becomes stiff, making it harder for the heart to pump blood throughout the body, resulting in poor quality of life and increased mortality.8 Patients with ATTR-CM normally experience shortness of breath, oedema, heart palpitations and fatigue.8 Life expectancy for patients with ATTR-CM is currently two to five years after diagnosis, highlighting the importance of early and accurate detection to slow disease progression.15
ATTRv-PN affects the function of the peripheral nerves, causing nerve damage. These patients often experience painful neuropathy in their hands and feet, motor disability including difficulty walking and falls, and gastrointestinal disturbances.15 About 30% of patients with ATTRv-PN have unexplained weight loss and 50% deal with urinary incontinence.5 Without swift implementation of a care plan, ATTRv-PN is generally fatal within 10 years, highlighting the need for earlier diagnosis and increased therapy options.12
While ATTRv-PN and ATTR-CM are distinct diseases, a majority of TTR mutations give rise to a mixed clinical phenotype, where both neurologic and cardiac impairments are present.16 Patients with mixed phenotype experience both cardiac and neurological symptoms and high mortality rates.16
Clinicians often face challenges diagnosing ATTRv-PN, ATTR-CM and mixed phenotype ATTR
Although several guidelines and expert consensus recommendations for diagnosing and managing care for ATTR are available and evolving, patients often face a difficult and complex journey toward getting the help they need.2-5,17 Because the symptoms of ATTR commonly mirror other conditions, patients are often required to visit several different physicians before receiving a correct diagnosis.2 For patients with ATTRv-PN alone, about 20 to 40% received multiple misdiagnoses before receiving an accurate one.5
It’s important for clinicians to try and rule out ATTR as soon as possible, but the methods for detecting ATTRv-PN, ATTR-CM and mixed phenotype are complex.
- Diagnosing ATTRv-PN starts with a clinical suspicion that includes the presence of rapidly progressive sensory motor neuropathy. The final step is to perform DNA sequencing and to perform a biopsy and amyloid typing.5
- Diagnosing ATTR-CM also starts with a clinical suspicion, based on ECG, echocardiogram, or cardiac magnetic resonance imaging.18 The next step is to rule out that the patient is suffering from amyloid light chain cardiac amyloidosis by performing a monoclonal protein screen. This is followed by performing a cardiac scintigraphy scan to detect the presence of amyloid and then genetic testing.18
- Diagnosing mixed phenotype happens when a patient is diagnosed with symptoms consistent with an ATTR-CM diagnosis and an ATTRv-PN diagnosis.19
At AstraZeneca, we’re advancing the science behind ATTR and raising awareness about the importance of detecting it and its related conditions as early as possible to quickly implement care plans for these patients. Diagnosing ATTR early increases their therapy options, leading to improved quality of life and patient outcomes. We’re committed to helping more people with ATTR in current and future generations to combat this devastating disease before it turns fatal.
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References
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Veeva ID: Z4-58800
Date of preparation: October 2023