How to Diagnose Transthyretin Amyloid Cardiomyopathy (ATTR-cm)

In a review article published by the American Heart Association, the authors stated "Diagnosis of ATTR-CM is often missed or mistaken as hypertrophic cardiomyopathy or heart failure with a preserved ejection fraction of unknown cause. Although considered a rare disease, the true prevalence of ATTR-CM is unclear and is likely higher than appreciated."

"But more recently that we know that amyloid is more prevalent than we once thought. And so therefore we need to diagnose it"  Dr. Philip Weintraub, a cardiologist at NYU Langone Health, tells SurvivorNet.

In previous years, obtaining a conclusive ATTR-cm was particularly challenging because back then doctors relied on taking a biopsy from the heart tissue which was a very invasive procedure with possible side effects. However, now is not the case.

Recently, ATTR-cm has gained a lot of recognition among the medical community and new techniques were developed to ease the identification and diagnosis of this condition. This is very good news because early diagnosis means early treatment and better patient outcomes.

A study published in the Journal of Current Oncology Reports in 2021, restates these claims as the authors say "There are now readily accessible, accurate, noninvasive diagnostic tests for cardiac amyloidosis as well as therapies to improve symptoms and survival."

What Is Transthyretin Amyloid Cardiomyopathy (ATTR-cm) What You Need to Know

Transthyretin amyloid cardiomyopathy (ATTR-cm) is an extremely rare, progressive, and life-threatening disease that affects the heart. It happens due to the accumulation of an abnormal transthyretin protein (TTR protein). Under normal conditions, this protein transports vitamin A and thyroxin hormone (from the thyroid gland) to the liver. But ATTR-cm patients, have a faulty protein that folds incorrectly on itself producing amyloid clumps in fibrils structure that deposits in the heart as well as other organs.

There are two types of transthyretin amyloid cardiomyopathy, these are:

1. Hereditary transthyretin amyloid cardiomyopathy (hATTR-cm) This type of ATTR-cm generally runs in families, where they carry a mutated variant of the TTR gene which produces the abnormal transthyretin protein leading to its deposition. Symptoms for patients with hATTR-cm may appear anytime between 20-80 years old.
2. Wild-type transthyretin amyloid cardiomyopathy (wATTR-cm) This type of ATTR-cm appears sporadically and is closely associated with old age. Thus, symptoms generally appear in patients older than 65 years old.

You should be clear with your doctor about all the signs and symptoms you're experiencing to help them make a diagnosis.

Below is a list of the most common symptoms of transthyretin amyloid cardiomyopathy (ATTR-cm):

• Shortness of breath (especially during inactivity or lying down)
• 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

Nevertheless, not every patient will experience the same symptoms. Some may experience these symptoms in severe forms while others may have milder symptoms or no symptoms at all, this all depends on the following criteria:

• Type of ATTR-cm (hereditary or wild-type)
• Age of the patient
• Overall health of the patient
• Other underlying medical conditions

Transthyretin Amyloid Cardiomyopathy (ATTR-cm) Diagnosis

Dr. Weintrub explains "To diagnose the disease one much, take a thorough history, do a complete physical exam, obtain objective studies, including an electrocardiogram and an echocardiogram, and therefore be able to, through those modalities put together a working diagnosis."

The first thing your doctor will do is check your medical history, perform a clinical examination, and evaluate your signs and symptoms. After that, they may proceed with prescribing the appropriate diagnostic tests.

The diagnostic tests available for transthyretin amyloid cardiomyopathy include the following:

1. Blood tests

This test is done to determine which type of transthyretin amyloid cardiomyopathy (ATTR-cm) a patient has: hereditary ATTR-cm or wild-type ATTR-cm. In this test, the TTR gene (transthyretin gene responsible for producing transthyretin protein) is examined to identify whether it's mutated or not.

Patients with hereditary ATTR-cm should consult a genetic counselor, especially if they're planning to have children.

2. Cardiac Magnetic Resonance Imaging (Cardiac MRI)

Cardiac MRI uses radio waves and takes images of the heart to look for any abnormalities caused by ATTR-cm. These abnormalities result from the deposition of amyloid fibrils on the heart which will result in a thicker and stiffer heart. Your doctor will look for any changes like enlargement of the atria or thicker heart chambers.

3. Cardiac Pyrophosphate (PYP) Scan

In this test, a radioactive material called pyrophosphate will be injected into your blood. It should reach your heart after approximately an hour. The science behind this test is that the radioactive pyrophosphate binds with the clumped amyloid proteins and lights up the screen of the computer to which it's connected revealing the presence of these abnormal misfolded proteins.

A study published in the Journal of Nuclear Cardiology in 2021, studied the value of pyrophosphate in diagnosing transthyretin amyloid cardiomyopathy (ATTR-cm) and revealed that it showed great accuracy not just in identifying ATTR-cm but also in monitoring the progress of the disease. The authors say "Quantitative assessment of myocardial radiotracer activity with pyrophosphate has high diagnostic accuracy for ATTR-CM."  They also added that "Pyrophosphate is a potential non-invasive marker in ATTR-CM to follow the progression of disease or response to medical therapy."

4. Echocardiogram

In this test, ultrasound (sound waves) is used and makes images of your heart to evaluate your heart and whether it's stiffer and thicker or not (determine the speed and direction of blood flow).  To get a better look at the effect of ATTR-cm on the heart, your doctor may combine an echocardiogram with something called strain imaging to determine if any amyloid protein deposits have affected the heart muscle causing damage.

5. Electrocardiogram (ECG) or (EKG)

Dr. Dwivedi tells SurvivorNet, "The common ways to diagnose ATTR-CM is starting with and ECG (electrocardiogram) and a physical exam." In this test, your heart's electrical signals are recorded to determine the electrical and conductive functionality of the heart. This may reveal some abnormalities like fibrillation (heartbeat irregularities) or arrhythmias.

6. Biopsy of the Heart

In this test, a small sample of your heart muscle is excised through a procedure where a catheter is inserted and directed towards the heart to take a small piece of the tissue to be examined under the microscope for abnormalities. However, this is considered an invasive procedure and is rarely done today.

It's important to note that these diagnostic procedures do not confirm an ATTR-cm diagnosis conclusively, but they give your doctor better informative insight into your heart condition so that they can best assess your condition and recommend the best management or treatment plan for you.

The Bottom Line

Early diagnosis and treatment for transthyretin amyloid cardiomyopathy (ATTR-cm) are crucial to an improved prognosis and better quality of life for its patients.

There are many advanced and noninvasive techniques available to identify and diagnose ATTR-cm. Additionally, researchers are consistently trying to come up with better diagnostic tests with higher specificity and sensitivity as well as discover a treatment that's both safe and effective for ATTR-cm patients.

If you have transthyretin amyloid cardiomyopathy (ATTR-cm), you should follow up with your doctor regularly so that they can closely monitor your condition and recommend the best treatment plan suitable for you.

Questions to Ask Your Doctor

• What causes ATTR-cm?
• Which type of ATTR-cm do I have?
• What are the symptoms associated with this disease?
• What's the most conclusive diagnostic test available?
• Are there any side effects to a specific diagnostic test?
• What's the difference between invasive and noninvasive diagnostic techniques?
• How can ATTR-cm be treated?
• How can I improve my life expectancy?
• What are the side effects associated with each treatment?
• Are there any clinical trials suitable for me?

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