Transthyretin amyloid cardiomyopathy (ATTR-cm) affects both women and men (although more prevalent in men). Symptoms typically begin to appear between the ages of 30-50 and vary depending on which type of ATTR-cm a person has. In some cases, the symptoms may be mild and may go unnoticed for several years. In other cases, however, symptoms may be severe and life-threatening.

A study published in 2022, in the Methodist Debakey Cardiovascular Journal, conclude that there are certain factors at play when it comes to the conclusive identification of the signs and symptoms of transthyretin amyloid cardiomyopathy (ATTR-cm). Among these most important factors are the different transthyretin variants and types of the disease.

The authors put it in their paper as follows "There is considerable heterogeneity in the clinical presentation, and phenotypic heterogeneity is dependent on both genetic and environmental factors. Early diagnoses, recognition of the early stages of cardiac infiltration, and initiation of treatment are essential to optimize long-term prognosis."

This simply means that early diagnosis and treatment are the keys to getting favorable results when it comes to the life expectancy and survivorship of ATTR-cm patients. The first step to an optimal treatment plan is to evaluate the symptoms and determine which type of ATTR-cm a patient has.

Evidently, two types of transthyretin amyloid cardiomyopathy will present with varying degrees of symptoms, these include the following:

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.

A genetic test may be done for those who present with a family history of ATTR-cm or heart failure symptoms to conclusively confirm the diagnosis.

This was concurred by a review study published in 2019 in the Current Heart Failure Reports, where the researchers concluded that genetic considerations should be implemented in the diagnostic and treatment aspects of the disease.

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.

Unfortunately, patients with (wATTR-cm) may not exhibit any signs and symptoms of the disease until it's very late and the disease has already caused irreversible damage (ex. Heart failure).

Signs and Symptoms of ATTR-cm

Symptoms of ATTR-cm will differ from patient to patient depending on several factors, these include the following:

• Type of the disease (wild or hereditary ATTR-cm)
• Location and extent of abnormal protein deposition
• Overall health and age of the patient
• Patient's previous medical history

Below is a list of the signs and symptoms of ATTR-cm:

• Shortness of breath, especially during times of inactivity this happens because the abnormal protein starts accumulating in the heart muscle which makes the heart thicker and stiffer making it hard to pump blood resulting in fluid backing up in the lungs
• Irregular heartbeats (arrhythmias especially atrial fibrillation) happen when the abnormal protein deposits on the conduction system of the heart leading to irregularities. May be associated with fainting, palpitations, or a feeling of giddiness.
• Dizziness due to heart block
• Tingling, numbness, pain in the arms, legs, or, feet the scientific name for it is peripheral neuropathy which means that your nerves are affected
• Edema (swelling in the legs due to fluid retention)
• Tiredness and extreme fatigue
• Chest pains usually a sign of heart failure, patients should seek immediate care

These signs and symptoms can often be misleading for doctors because in the initial stages they resemble other conditions that are unrelated to heart diseases and in the late stages, they are so similar to heart failure that they're often mistaken for it. So, doctors need to suspect ATTR-cm to reach a diagnosis.

Moreover, the presenting symptoms for patients with hereditary ATTR-cm will not be the same as patients with wild-type ATTR-cm. Generally, patients with wild-type ATTR-cm don't experience any symptoms until the disease has progressed into the very late stages.

“You can have any symptom; chest pain, shortness of breath, palpitation, which could be indicative of future rhythm disturbances," said Dr. Philip Weintraub, a cardiologist at NYU Langone Health.

Dr. Weintraub adds "In terms of the more generalized symptoms you could have lightheadedness, you could have fatigue, but a lot of that is based upon the fact that without the necessary oxygen that needs to be in your bloodstream, it’ll compromise your ability to do," he said.

Diagnosis of ATTR-cm

After careful examination and suspecting transthyretin amyloid cardiomyopathy, your doctor will prescribe the following tests to get a conclusive diagnosis:

• Echocardiogram a type of ultrasound scan to check the heart and neighboring blood vessels
• Electrocardiogram a test to check your heart's electrical activity and rhythm, it's also referred to as ECG
• Cardiac MRI
• Taking a biopsy from the heart muscle a medical procedure where a small sample from the heart muscle is excised and examined under the microscope
• Screening for mutated TTR gene (for the hereditary type hATTR-cm)

Depending on the results of these tests, your doctor will proceed with prescribing the most appropriate treatment for you, this can include any of the following:

• Medications that stop further protein depositions
• Medications to relieve symptoms caused by other complications like heart failure or carpal tunnel syndrome
• Tafamidis or Vyndamax Drugs that specifically target the TTR gene to stop proteins from folding abnormally
• Inotersen or Tegsedi Drugs to slow the production of amyloid protein by the liver
• Organ transplantation surgery (Liver, kidney, or heart transplant) depending on the affected organ

"Number one would be to see your doctor regularly," Dr. Dwivedi says "It is important to seek medical care for this condition, because we have good options and can change lives. Second would be talk to your doctor if any of your symptoms change. You would rather know sooner rather than later, before things get worse and when you may need hospitalization."

Also, seeking support whether from loved ones or other patients who may be going through the same thing you are is pivotal in making your disease journey easier and more informed. The American Heart Association offers a support network to connect with other ATTR-cm patients where you can check these resources and learn about patient stories.

The Bottom Line

The signs and symptoms of transthyretin amyloid cardiomyopathy (ATTR-cm) are typically non-specific and share clinical features with many other disease conditions. Thus, it has contributed to the underdiagnosis of ATTR-cm.

ATTR-cm presents with heart failure symptoms. When symptoms first start to appear, they may seem similar to common conditions like asthma or high blood pressure. Nevertheless, it's important to consult with a doctor so that these symptoms can be properly evaluated. If someone in your family has been diagnosed with ATTR-cm, your doctor may suggest that you undergo genetic testing.

Questions to Ask Your Doctor

• Which type of transthyretin amyloid cardiomyopathy (ATTR-cm) do I have?
• What are the symptoms associated with this disease?
• Should I be monitored for heart failure?
• How can ATTR-cm be treated?
• What are the disease complications and how can I avoid them?
• Will I need organ transplantation at any point during my disease?
• How can I improve my life expectancy?
• What are the side effects associated with each treatment?
• Are there any clinical trials suitable for me?
• Where can I contact other patients with ATTR-cm that are going through the same thing I'm going through?

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