Newly Diagnosed with Transthyretin Amyloid Cardiomyopathy (ATTR-cm)? Here's What You Need to Know

• Shortness of breath
• Irregular heartbeats (arrhythmias especially atrial fibrillation)
• Edema (swelling in the legs due to fluid retention)
• Tiredness and extreme fatigue
• Dizziness
• Fainting
• Bloated stomach
• Coughing and wheezing
• Confusion
• Disorientation

Transthyretin Amyloid Cardiomyopathy (ATTR-cm) At A Glance

• Transthyretin. Normally, this protein functions in transporting vitamin A (retinol) and thyroxine hormone (from the thyroid gland) to the liver. When mutated, it folds on itself, and forms clumps known as amyloid fibrils that deposit on organs making them stiffer and thicker.

• Amyloid. Refers to the protein fibrils that are misfolded and start building on several organs, in the case of ATTR-cm, these clumps accumulate on the walls of the heart rendering them stiffer and unable to perform their normal function. As time goes by, these protein deposits increase which in turn leads to more damage.

• Cardiomyopathy. A term that means heart muscle disease making it unable to perform its normal function.

In ATTR-cm, amyloid fibrils are built up in your heart which means that it hinders this process (relaxing and contracting) by blocking the heart, backing blood in the lungs, or disrupting the normal coordination of blood flow in the body which in turn leads to serious and even deadly complications like heart failure if it goes unchecked for a long time.

There are two types of transthyretin amyloid cardiomyopathy (ATTR-cm) and they differ in the cause or etiology of their disease, these are:

1. Hereditary Transthyretin Amyloid Cardiomyopathy (hATTR-cm) 

Hereditary ATTR-cm stems from a genetic factor mutation in the gene responsible for producing transthyretin protein where a faulty variant of the gene is inherited from generation to generation. Patients with hATTR-cm are at an advantage of being diagnosed early on if they are familiar with their family history.

Those who have any of the following characteristics are more susceptible to developing hereditary ATTR-cm:

• Family history of ATTR-cm or heart failure
• TTR gene mutation (mutation in the gene responsible for producing transthyretin protein leading to its deposition in the heart as well as other organs)
• Sex Males are more prone to developing hATTR-cm than females
• Race African Americans
• Older age > 50 years old (although it's possible to have symptoms anywhere between the ages of 20-80 years old)

Thus, those who have a family history of hATTR-cm are advised to have their genes tested early on to stay ahead of any risks associated with the abnormal gene. Additionally, if they're planning to create a family and have children, they should seek the consultation of a genetic counselor beforehand to be able to prevent this gene from passing on.2

2. Wild-type Transthyretin Amyloid Cardiomyopathy (wATTR-cm) 

Wild-type ATTR-cm stems from an environmental factor the abnormal protein start to randomly misfold and deposit usually associated with old age.

Those who have any of the following characteristics are more susceptible to developing wild-type ATTR-cm:

• Age > 65 years old
• Sex Males are more prone to developing wATTR-cm than females

Studies have shown that the wild-type ATTR-cm has a progressively worse prognosis than hereditary ATTR-cm. Presumably, the survival rate for wild-type ATTR-cm is approximately 3.5 years while for hereditary ATTR-cm is between 2-5.5 years.

How to Diagnose and Treat ATTR-cm

"ATTR cardiomyopathy is, unfortunately, an underdiagnosed condition," says Dr. Aeshita Dwivedi, a cardiologist at Lenox Hill Hospital in New York.  "And as physicians, we always have to maintain a high suspicion for this disease." To diagnose ATTR-cm, your doctor may first order these tests to assess the function of your heart and look for signs that something is wrong, these include the following:

• Clinical examination
• Imaging studies cardiac magnetic resonance imaging (MRI)
• Genetic testing (if it's hereditary transthyretin amyloid cardiomyopathy, testing the TTR gene responsible for producing transthyretin protein)
• Cardiac pyrophosphate scan (PYP) a doctor injects radioactive pyrophosphate into your arm and connects it to a screen, when there's accumulated amyloid the screen lights up
• Electrocardiogram or ECG a test to check your heart's electrical activity and rhythm
• Echocardiogram used sound waves to check the heart and neighboring blood vessels, their thickness, and how it pumps blood
• Taking a biopsy from the affected organ (biopsy from the heart muscle) and examining it under the microscope. However, this is currently rarely applied

"Recently we've learned that amyloid is more prevalent than we once thought," Dr. Philip Weintraub, a cardiologist at NYU Langone Health tells SurvivorNet. "And so therefore we need to diagnose it. Its presence can be isolated using what's called a MUGA scan, that can demonstrate certain properties that are lost in terms of the heart's ability to relax."

After receiving a conclusive diagnosis for transthyretin amyloid cardiomyopathy (ATTR-cm), your doctor may begin to prescribe appropriate treatment options to help alleviate the symptoms and manage your condition.  These can include one or more of the following treatments:

• Medications to relieve symptoms caused by other comorbidities like heart failure, or arrhythmias
• Drugs that specifically target the TTR gene to stop proteins from misfolding (ex. tafamidis or vyndamax)
• Medications to slow the production of amyloid protein by the liver (ex. Inotersen or Tegsedi)
• Organ transplantation (Liver, kidney, or heart transplant) this happens in rare instances in advanced stages of the disease
• Other treatment options include supportive practices like surgery or dietary changes

You should consult your doctor on the best treatment option for you and inquire about the risks and side effects associated with each option. Also, you can ask about enrolling in clinical trials and whether you're the right candidate for it, if this is something you want.

Life Expectancy and Survivorship for Patients with ATTR-cm

Since there's no cure yet for transthyretin amyloid cardiomyopathy (ATTR-cm), most of the treatment options available only help with relieving the symptoms and slowing the progress of the disease. However, any damage already caused by the abnormal protein deposition prior to getting the diagnosis is irreversible.

Thus, the life expectancy for patients with ATTR-cm will significantly depend on the time of the diagnosis, and the response to treatment.

• The life expectancy for patients with ATTR-cm who receive treatment ranges approximately between 2-6 years from diagnosis.
• As for those who don't receive treatment, their life expectancy ranges between 2-3.5 years from the time of diagnosis.

A study published in the Journal of Comparative Effectiveness Research in 2021, states that the timely diagnosis and treatment for patients with ATTR-cm with tafamidis are predicted to significantly improve their survival and quality of life.

Similarly, another study was published in the European Heart Journal. Quality of Care and Clinical Outcomes in 2022, claims that tafamidis is expected to more than double the life expectancy of ATTR-CM patients compared to other treatments.

ATTR-cm How Can You Improve Your Life Expectancy?

To improve your life expectancy if you're living with a diagnosis of transthyretin amyloid cardiomyopathy, you can do the following practices:

• Share all the symptoms that you're experiencing with your doctor even if you think that something isn't important
• Ask your doctor about ways to improve your quality of life whether it's in your diet or everyday routine
• Follow the guidance of your doctor and stay up to date with all relevant information about your condition
• Take care of your mental health as it can take a toll on your physical health, if you're feeling depressed or anxious, try to find ways to decompress. The American Heart Association offers a support network to connect with other ATTR-cm patients, benefit from their experience, and help others as well. Additionally, you can check on these patients and learn about their success stories.

The Bottom Line

Diagnosing transthyretin amyloid cardiomyopathy (ATTR-cm) remains a challenge for most clinicians. This is primarily due to the similarities of ATTR-cm symptoms with other conditions. So, despite being a serious and life-threatening disease, getting that diagnosis is the first step to getting the right treatment and leading a better life.

Time is very important for patients with ATTR-cm where the faster they get a diagnosis, the quicker they can receive treatment that will slow the disease from progressing and prevent major organ damage.

Many studies have proved the positive effect of 'tafamidis' for improving the life expectancy and survivorship of patients with ATTR-cm, additionally, there are several clinical trials underway to discover a better treatment option with curative capabilities.

Questions to Ask Your Doctor

• Do I have hereditary ATTR-cm or wild-type ATTR-cm?
• What are the symptoms associated with this disease?
• What are the pros and cons of taking tafamidis?
• What is my life expectancy and how can I prolong it?
• What are other treatment options available for ATTR-cm?
• What are the disease complications and how can I avoid them?
• Are there any clinical trials suitable for me?
• Are there any support groups for ATTR-cm patients?

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