Taming Wild-Type Amyloidosis — FAQ

Leading cardiologist Dr. Martha Grogan was our guest speaker for Taming Wild-Type, our recent ARC Talks webinar focused on wild-type transthyretin amyloidosis (ATTRwt). In the presentation, Dr. Grogan, the Founder and Director of the Cardiac Amyloid Clinic at the Mayo Clinic, discussed disease progression, prognosis, treatment options, and more. You can watch the webinar in its entirety here.

Dr. Grogan provided very helpful information during the webinar and answered many of the questions asked during the Q&A portion of the presentation.

We compiled those answers as a resource below:

Wild-type ATTR Amyloidosis FAQ:

Wild-type Amyloidosis – An Overview:

Q: What percent of the people over the age of 75, start producing Wild-Type Amyloid proteins?
A: The true incidence or wild type amyloidosis is unknown. It is thought to be very underdiagnosed. However, there are various studies underway that aim to ascertain this information.

Q: Is there any idea of what factors are connected with or might cause wtATTR?
A: Little is known why some people develop wild-type amyloidosis and not others. Research is being done to understand what factors might cause “wild’-type ATTR.

How Wild-Type Can Affect Parts of the Body:

Q: In addition to the heart, can wild-type ATTR affect other organs or parts of the body?
A: Wild-type ATTR can affect other organs or parts of the body (besides the heart). Most commonly it affects the carpal tunnel and spinal ligaments and occasionally the bladder and gastrointestinal tract. However, amyloid deposits may be found almost anywhere in the body.

Q: If you have TTR in one organ, such as the colon, is it likely to spread to other organs?
A: It is unknown if TTR is likely to spread to other organs. Some patients may have small deposits of TTR that do not progress and cause additional symptoms.

Wild-type Amyloidosis – Diagnosis & Treatment:

Q: How can I verify my diagnosis and start receiving treatment?
A: In order to verify your diagnosis, it is recommended that you seek an evaluation at an amyloid center.

Editor’s note: To help find an amyloid center near you, join MyAmyloidosisPathfinder (MAP) or contact ARC at arc@arci.org or 617-467-5170.

Q: Should patients with documented bilateral carpal tunnel syndrome, biceps tendon rupture, and lumbar spinal stenosis be contacted for fat pad aspiration for congo red staining to test for amyloidosis?

A: This requires clinical correlation. Algorithms are being developed to alert clinicians. However, conditions such as carpal tunnel (even bilateral) and spinal stenosis are very common, not all are due to amyloid, perhaps not even the majority. Various studies are currently underway to understand this better.

Q: Is carpal tunnel surgery recommended?
A: Carpal tunnel surgery can help relieve symptoms, an expert will be able to provide recommendations on whether to have surgery. In mild cases, a wrist splint, physical therapy, or steroid injections in the wrist may help reduce symptoms.

Q: Are heart transplants commonly done for wild-type ATTR?
A: Heart transplants can be done for wild-type ATTR, however they are not very common and are usually only considered for those who are under 70 years of age.

Q: After a heart transplant, how quickly will the amyloidosis infiltrate the cardiac muscle and cause an impact on cardiac function?
A: It is not currently known how long it will take for amyloid deposition to affect the transplanted heart. However, most patients do well with their new heart. Treatment is individualized, and some patients may receive medications to try to prevent amyloid production and deposition in the heart, especially if amyloid is present elsewhere.

Drug Development & Clinical Trials for Wild-type Amyloidosis: 

Q: Are there any new drugs being tested to remove the amyloid deposits?
A: There is currently no proven medication to remove amyloids, though some are under investigation in clinical trials.

Q: Why do the drug development teams seem to focus on hereditary ATTR over wild-type for clinical trials research?
A: Drug development companies made the initial decision to focus on hereditary ATTR, however they are now focusing on ATTR “wild” type trials as well.

Editor’s Note: Below is additional information about drug development and clinical trials provided by ARC’s research team:

• Vyndamax/Vyndaqel, a TTR stabilizing drug, was approved by the FDA in 2019 for patients with  hereditary and wild-type ATTR cardiomyopathy.
• Patisiran, vutrisiran, and eplontersen are gene-silencing drugs that are currently in phase 3 clinical trials for patients with hereditary and wild-type ATTR cardiomyopathy, as is acoramidis, a TTR stabilizer.
• NTLA-2001 is a CRISPR/Cas9-based gene editing drug in Phase 1 clinical trials that just recently began enrolling wild-type patients.
• PRX004 is an amyloid-targeting monoclonal antibody that is expected to begin phase 2 studies in hereditary and wild-type ATTR cardiomyopathy patients later this year, whereas NI006 is another amyloid-targeting monoclonal antibody currently in Phase 1 clinical trials for the same population.

Managing the Symptoms of Wild-type Amyloidosis:

Q: Is lower back pain common and how do you know if it is caused by amyloid?
A: Spinal stenosis may cause back pain, otherwise usually it is unrelated.

Q: What can be done to relieve neuropathy?
A: Supportive treatments can be helpful in relieving symptoms caused by neuropathy; these can include gabapentin and other drugs as prescribed by neurologist. (In the ARC Talks webinar, Amyloid Neuropathy Burden and Management, Dr. Kelsey Barrell from the University of Utah offers suggestions to help manage neuropathy symptoms.)

Q: Is it common for ATTR to cause any pressure and or tightness in the stomach area?
A: ATTR does not directly cause pressure in the stomach area, however this can occur with fluid build-up.

Q: Can edema be treated?
A: Yes edema can be treated with diuretics. It is recommended that you discuss this with your providers, as they can make recommendations diuretic dosing, as well as optimizing sodium intake and hydration to manage edema. Compression stockings may also help relieve lower leg swelling.

Q: Can shortness of breath be improved?
A: Yes, shortness of breath can be improved with diuretics and medical management.

Diet & Exercise as it Relates to ATTR Amyloidosis:

Q: Is there a recommended diet for ATTR patients? Is the goal to consume minimal protein of any kind, or simply to avoid those that come from meats?
A: To clarify the dietary guidelines, there is no need to limit or withhold any protein. Depending on a patient’s cardiac symptoms, it may be advised to lower sodium intake, and patients should work with their providers for specific guidance.

Q: Are there any studies and/or research that has been conducted on the use of green tea extract in treatment of ATTR?
A: There have been small studies on green tea extract, however it has shown no benefit in extending survival. It is important to note that green tea can interfere with warfarin and has many other drug interactions.

Q: How important is exercise in keeping your heart as strong as possible? (Long walks? Walking up inclines, etc.)
A: Exercise is important to keep your heart strong, however it does not affect amyloid directly. It is recommended to be active, but never to the point of exhaustion.

A Look at Wild-type Patient Outcomes:

Q: If I have wild-type amyloidosis how long will I live?
A: Before we had treatment the “average” patient with wild-type TTR lived about 3.5 years after diagnosis. These patients were often diagnosed late and quite sick at time of diagnosis. We can use a staging system to get an idea of prognosis but these systems do not take treatment into account (they were developed before tafamidis), additionally other factors play a role, such as the existence of other illnesses or conditions.

If you have any questions about the information presented above, please email arc@arci.org. Additional information about wild-type can also be found here.