Wild-type Amyloidosis
From Amyloidosis Foundation.com
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Wild-type ATTR is also referred to as ATTRwt. It is not hereditary. This disease used to be called SSA, which stood for Senile Systemic Amyloidosis, which is now an outdated term.
Deposits of TTR amyloid can be found throughout the body, so it is a systemic amyloidosis disease, with significant clinical involvement most commonly found in the heart. Wild-type ATTR is also common in carpal tunnel, which can be the first (early) symptom. This is a disease that is almost exclusively a disease of men, originally reported in those age of 80 and over. As research continues, wild-type ATTR has been increasingly found in individuals in their early 60s. It is often overlooked as an amyloidosis disease because so many people experience heart problems in their later years. It is called wild-type ATTR because the misfolding and depositing amyloid protein comes from transthyretin protein without a genetic mutation, referred to as “wild-type” because it is the natural form of this protein. These deposits can interfere with the heart’s normal function, causing heart rhythm problems and heart failure. |
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Symptoms
Cardiomyopathy means a disorder or disease of the heart muscle. Congestive heart failure, and an irregular heart rhythm called atrial fibrillation, are the most common symptoms.
Amyloid deposits in the heart can make the heart unable to function efficiently. This may result in shortness of breath, dizziness, or edema (swelling, especially in the legs). Some symptoms may occur with only minor activity. Amyloid can also affect the electrical system of the heart, causing the normal heartbeat to speed up or slow down. This is known as arrhythmia. During atrial fibrillation, the abnormal heart rhythm usually causes rapid and irregular beating.
For some older men, a history of carpal tunnel syndrome (especially without a clear cause), along with heart problems, is a signal to the doctor to consider testing for wild-type ATTR. To a lesser extent, wild-type ATTR has shown amyloid deposits in the lungs, bladder, and bowel, often with no, or minor, symptoms for the patient; although some patients have extensive bladder involvement that can lead to hematuria (blood in the urine).
In addition, peripheral neuropathy symptoms are present in a small number of patients, and spinal stenosis has also been found to be related to wild-type ATTR. Spinal stenosis narrows the spaces in the backbone and puts pressure on the spinal cord and nerves. Symptoms are caused by the pressure on the nerve root, causing pain that occurs mainly along the back of the leg.
Diagnosis
Since wild-type ATTR and many other amyloidosis diseases can cause cardiomyopathy in this older male age group, is it extremely important to identify the type of amyloid. A patient with AL (light chain) Amyloidosis who shows cardiomyopathy symptoms will often be treated with chemotherapy – and this is not the right treatment for wild-type ATTR patients with cardiomyopathy. For this reason, medical investigation is needed and the diagnosis of the type of amyloid must be correct.
For wild-type ATTR, it is difficult to get a positive diagnosis for amyloid deposits in tissues other than the heart. If a patient’s echocardiogram results (heart test) show signs of complications, then, in many cases, a biopsy of the heart tissue is needed to get an accurate diagnosis. However, studies of newer heart scans for wild-type ATTR are ongoing and may replace the need for heart biopsy in the future.
If a biopsy of the heart tissue is obtained, then this biopsy tissue is sent to a lab for Congo-red staining. The lab will stain the biopsy and, if it turns an apple green color under a ‘polarizing’ microscope, then amyloidosis is confirmed. The lab will also take the biopsy tissue and run a protein sequence analysis test to see which type of protein is affected. If this test shows that the transthyretin (TTR) protein is involved, then a simple blood sample is sent to a lab and experts do a genetic sequencing test to examine the DNA chains.
If this TTR genetic sequencing test produces no identifiable mutations, then wild-type ATTR is the resulting diagnosis. So you can see that it takes several steps and a doctor must continue testing until an accurate diagnosis is achieved.
These heart tests can help with diagnosing and monitoring heart stress or damage, as well as response to treatment:
Blood tests to look for stress and strain on the heart are useful in many forms of heart disease, including wild-type ATTR. The cardiac biomarkers that are used include troponin T or troponin I, and NT-proBNP (which stands for N-terminal pro-brain natriuretic peptide) or BNP (brain natriuretic peptide). Different laboratories use one versus the other.
The echocardiogram (also called echo”) is an ultrasound of the heart. A doctor can look at the size and shape of the heart, and whether it is relaxing normally in between heartbeats. Amyloid cannot be seen directly, but it does make the heart larger and stiffer than normal.
Recently, other imaging tests for the heart have also shown to be useful. One test is the MRI (magnetic resonance imaging), and, in this instance, is also referred to as CMR (for cardiac magnetic resonance). Pyrophosphate scanning, a nuclear medicine test, is also used to evaluate whether an unusual type of abnormality of heart muscle function (“cardiomyopathy”) is present. Current data suggests this scan may be useful in distinguishing different types of amyloid heart disease. Many experts agree that wild-type ATTR is underdiagnosed.
Treatment
Many of the same treatments used for other ATTR diseases that involve cardiomyopathy can be applied to wild-type ATTR. Trial drugs for ATTR, such as tafamidis and diflunisal, are sometimes considered for wild-type ATTR patients. There have been advances in research that are studying the ‘silencing’ of gene expression through the addition of stranded RNA. This is called RNAi (meaning RNA interference). New medications are in development that include RNAi therapy, targeting transthyretin (TTR). Eventually some of these new medications may be options for patients with wild-type ATTR.
Typically, for heart problems, diuretics can be prescribed to increase urination, which helps to decrease fluid retention in the body. As with all amyloidosis diseases, the use of diuretics for an amyloid heart condition must be carefully controlled by your doctor.
Since it is common for there to be no other major organ involvement other than the heart with wild-type ATTR, a heart transplant is a treatment option if severe cardiac involvement is present.
Small studies have been looking at a component of green tea to slow progression of the TTR-related diseases that involve the heart. Curcumin, a component of the spice tumeric, has shown some promise in decreasing TTR deposition. In addition, studies continue with “genistein,” which is a component of soy. Research may continue in these areas. Always consult with your doctor before considering any dietary changes.
Cardiomyopathy means a disorder or disease of the heart muscle. Congestive heart failure, and an irregular heart rhythm called atrial fibrillation, are the most common symptoms.
Amyloid deposits in the heart can make the heart unable to function efficiently. This may result in shortness of breath, dizziness, or edema (swelling, especially in the legs). Some symptoms may occur with only minor activity. Amyloid can also affect the electrical system of the heart, causing the normal heartbeat to speed up or slow down. This is known as arrhythmia. During atrial fibrillation, the abnormal heart rhythm usually causes rapid and irregular beating.
For some older men, a history of carpal tunnel syndrome (especially without a clear cause), along with heart problems, is a signal to the doctor to consider testing for wild-type ATTR. To a lesser extent, wild-type ATTR has shown amyloid deposits in the lungs, bladder, and bowel, often with no, or minor, symptoms for the patient; although some patients have extensive bladder involvement that can lead to hematuria (blood in the urine).
In addition, peripheral neuropathy symptoms are present in a small number of patients, and spinal stenosis has also been found to be related to wild-type ATTR. Spinal stenosis narrows the spaces in the backbone and puts pressure on the spinal cord and nerves. Symptoms are caused by the pressure on the nerve root, causing pain that occurs mainly along the back of the leg.
Diagnosis
Since wild-type ATTR and many other amyloidosis diseases can cause cardiomyopathy in this older male age group, is it extremely important to identify the type of amyloid. A patient with AL (light chain) Amyloidosis who shows cardiomyopathy symptoms will often be treated with chemotherapy – and this is not the right treatment for wild-type ATTR patients with cardiomyopathy. For this reason, medical investigation is needed and the diagnosis of the type of amyloid must be correct.
For wild-type ATTR, it is difficult to get a positive diagnosis for amyloid deposits in tissues other than the heart. If a patient’s echocardiogram results (heart test) show signs of complications, then, in many cases, a biopsy of the heart tissue is needed to get an accurate diagnosis. However, studies of newer heart scans for wild-type ATTR are ongoing and may replace the need for heart biopsy in the future.
If a biopsy of the heart tissue is obtained, then this biopsy tissue is sent to a lab for Congo-red staining. The lab will stain the biopsy and, if it turns an apple green color under a ‘polarizing’ microscope, then amyloidosis is confirmed. The lab will also take the biopsy tissue and run a protein sequence analysis test to see which type of protein is affected. If this test shows that the transthyretin (TTR) protein is involved, then a simple blood sample is sent to a lab and experts do a genetic sequencing test to examine the DNA chains.
If this TTR genetic sequencing test produces no identifiable mutations, then wild-type ATTR is the resulting diagnosis. So you can see that it takes several steps and a doctor must continue testing until an accurate diagnosis is achieved.
These heart tests can help with diagnosing and monitoring heart stress or damage, as well as response to treatment:
Blood tests to look for stress and strain on the heart are useful in many forms of heart disease, including wild-type ATTR. The cardiac biomarkers that are used include troponin T or troponin I, and NT-proBNP (which stands for N-terminal pro-brain natriuretic peptide) or BNP (brain natriuretic peptide). Different laboratories use one versus the other.
The echocardiogram (also called echo”) is an ultrasound of the heart. A doctor can look at the size and shape of the heart, and whether it is relaxing normally in between heartbeats. Amyloid cannot be seen directly, but it does make the heart larger and stiffer than normal.
Recently, other imaging tests for the heart have also shown to be useful. One test is the MRI (magnetic resonance imaging), and, in this instance, is also referred to as CMR (for cardiac magnetic resonance). Pyrophosphate scanning, a nuclear medicine test, is also used to evaluate whether an unusual type of abnormality of heart muscle function (“cardiomyopathy”) is present. Current data suggests this scan may be useful in distinguishing different types of amyloid heart disease. Many experts agree that wild-type ATTR is underdiagnosed.
Treatment
Many of the same treatments used for other ATTR diseases that involve cardiomyopathy can be applied to wild-type ATTR. Trial drugs for ATTR, such as tafamidis and diflunisal, are sometimes considered for wild-type ATTR patients. There have been advances in research that are studying the ‘silencing’ of gene expression through the addition of stranded RNA. This is called RNAi (meaning RNA interference). New medications are in development that include RNAi therapy, targeting transthyretin (TTR). Eventually some of these new medications may be options for patients with wild-type ATTR.
Typically, for heart problems, diuretics can be prescribed to increase urination, which helps to decrease fluid retention in the body. As with all amyloidosis diseases, the use of diuretics for an amyloid heart condition must be carefully controlled by your doctor.
Since it is common for there to be no other major organ involvement other than the heart with wild-type ATTR, a heart transplant is a treatment option if severe cardiac involvement is present.
Small studies have been looking at a component of green tea to slow progression of the TTR-related diseases that involve the heart. Curcumin, a component of the spice tumeric, has shown some promise in decreasing TTR deposition. In addition, studies continue with “genistein,” which is a component of soy. Research may continue in these areas. Always consult with your doctor before considering any dietary changes.