How is ATTR-cm Tested For?
- ATTR-cm is often difficult to diagnose, as it is an uncommon disease that is very complex. ATTR-cm also has similar symptoms to many common medical conditions.
- Several tests are ranging in type (noninvasive or invasive), and function used to diagnose ATTR-cm. The function of a test ranges from confirming an ATTR-cm diagnosis or ruling out another disease that may have the same symptoms as ATTR-cm.
- Your doctor needs to order diagnostic tests for ATTR-cm; thus, you must tell your doctor about all the symptoms you are experiencing so that they can order the most suitable tests.
The reasons behind an underdiagnosis of this condition are:
- low awareness among both doctors and patients due to its rarity
- this disease shares a lot of common symptoms with other conditions leading to a misdiagnosis at worst and a delayed diagnosis at best!
Transthyretin Amyloid Cardiomyopathy Causes, Types, and Symptoms
Transthyretin amyloid cardiomyopathy (ATTR-cm) is caused as a result of the continuous deposition of the abnormally folded transthyretin protein on the heart muscle.
Normally, transthyretin protein transports retinol (vitamin A) and a type of thyroid gland hormone called thyroxine to the liver, but sometimes this protein misfolds and forms clumps that are insoluble and accumulate. These clumps of misfolded proteins are called amyloid fibrils.
Dr. Philip Weintraub, a cardiologist at NYU Langone Health explains, "there can be many side effects because it is a systemic disease". The prognosis of ATTR-cm patients worsens with the continued amyloid deposition making early diagnosis and management key to improved patient outcomes.
There are two types of ATTR-cm, and they differ in their etiologies. These types include the following:
1. Hereditary Transthyretin Amyloid Cardiomyopathy (hATTR-cm). This type generally runs in families, and it's caused by a mutation in the transthyretin (TTR) gene, which produces a faulty protein that misfolds and deposits amyloid fibrils on the heart, nerves, kidneys, and other organs.
This faulty gene is inherited from generation to generation which is why it's recommended for those who carry the mutated variant of the TTR gene to seek genetic counseling first before deciding to conceive.
Symptoms of hereditary transthyretin amyloid cardiomyopathy (hATTR-cm) can start anytime between the ages of 20-80.
Risk factors for hereditary transthyretin amyloid cardiomyopathy (hATTR-cm) include the following:
- A family history of ATTR-CM or heart failure
- Old age (more than 50 years old), even though symptoms can appear between 20-80 years old
- Sex, males have it more than females
- Race, where it's more predominantly found in African Americans
2. Wild-type Transthyretin Amyloid Cardiomyopathy (wATTR-cm). This type is not inherited and doesn't run in families, but it's mostly associated with age. However, it also results from clumped proteins. It most commonly affects the normal functions of the heart and nerves, and, may cause other comorbidities like carpal tunnel syndrome (a condition that affects the hands causing pain, numbness, and tingling).
Symptoms of wild-type transthyretin amyloid cardiomyopathy (wATTR-cm) start after age 65.
Risk factors for wild-type transthyretin amyloid cardiomyopathy (wATTR-cm) include the following:
- Old age (above 65 years old)
- Males are more prone to getting wATTR-cm than females
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
Diagnostic Tests for Transthyretin Amyloid Cardiomyopathy (ATTR-cm)
There are several tests to diagnose transthyretin amyloid cardiomyopathy and they range in their function (whether to confirm the diagnosis of ATTR-cm or to rule out another disease) and type (invasive or noninvasive), they include the following:
1. TTR gene test A sample is taken from your blood or saliva
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, a blood sample is taken and the TTR gene (transthyretin gene responsible for producing transthyretin protein) is examined to identify whether it's mutated or not.
If the result of this test is positive (the TTR gene is in fact abnormal) then this means that the patient has hereditary ATTR-cm.
Patients with hereditary ATTR-cm will usually have a family history of heart failure or ATTR-cm. Additionally, it's recommended that they consult a genetic counselor, especially if they're planning to have children in the future.
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.
A 2019 study also notes that cardiac MRI may be especially helpful in making a diagnosis, however, an MRI is less useful in distinguishing ATTR-CM from basic amyloidosis, which is the buildup of amyloid in the heart or other organs unrelated to changes in transthyretin.
3. Nuclear Scintigraphy also called Cardiac Pyrophosphate (PYP) Scan A noninvasive imaging test
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.
This is generally done to rule out another type of amyloidosis called AL amyloidosis.
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)
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.
A 2021 report notes that the low-voltage result occurs in about 25 to 40 percent of ATTR-CM cases but helps rule out other causes of left ventricular hypertrophy.
6. Multigated Acquisition Scan (MUGA)
MUGA uses a radioactive tracer and a special camera to measure the pumping ability of the ventricles. It helps determine whether reduced pumping function may be related to a type of cardiomyopathy or other cause.
7. Endomyocardial Biopsy An invasive test that takes a sample from your heart muscle
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.
After getting a conclusive diagnosis, your doctor will prescribe the best treatment plan that's suitable for your case.
A study published in AHA Journals in 2019, concludes that the diagnosis of ATTR-CM is often mistaken for hypertrophic cardiomyopathy or heart failure and that the true prevalence of ATTR-CM is unclear and is likely higher than appreciated. The authors of this study recommend that doctors should consider the signs and symptoms experienced by patients with test results to reach an early diagnosis quicker.
They also add "To reduce the delays in diagnosis of this important health problem, specific programs for screening or early identification should be studied that leverage techniques having appropriate sensitivity and specificity as well as favorable cost/benefit." And they also reiterate the importance of early diagnosis by saying "Given that prognosis is highly dependent on the underlying cardiac dysfunction coupled with the recently available treatments for ATTR amyloidosis, screening programs may become important."
The Bottom Line
Transthyretin amyloid cardiomyopathy is an uncommon, life-threatening, progressive disease with a very high chance of getting misdiagnosed due to its similarity with other conditions like heart failure. Nevertheless, early diagnosis and treatment remain the best chance any ATTR-cm has for a better life expectancy and an improved quality of life.
There are many diagnostic tests for ATTR-cm patients, but your doctor has to suspect that you may have this disease first so that they can prescribe them and get a conclusive diagnosis. So, you must share with your doctor all the symptoms that you might be experiencing so that it can help guide them towards the best course of action suitable for you.
Questions to Ask Your Doctor
- Which type of transthyretin amyloid cardiomyopathy (ATTR-cm) do I have?
- What are the symptoms associated with this disease?
- What are the diagnostic tests available for ATTR-cm?
- Which diagnostic test is more accurate in determining ATTR-cm?
- What are the pros and cons of taking tafamidis?
- What are other treatment options available for ATTR-cm?
- What are the disease complications and how can I avoid them?
- How can I improve my life expectancy?
- Are there any clinical trials suitable for me?
- Are there any support groups for ATTR-cm patients?
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