Deep inside the liver, billions of protein molecules are produced every day. Sometimes, due to aging or genetic factors a particular protein, transthyretin (also known as prealbumin) can behave badly, misfolding into an unusual structure that can cause trouble throughout the body.
This can lead to a range of symptoms including shortness of breath, ongoing fatigue, tingling in the hands, and swelling in the legs. Often, patients seek care for these concerns from different specialists. They might visit an orthopedist to address carpal tunnel syndrome or a cardiologist to consider heart failure.
For these patients, seemingly unrelated issues may be clues to a single, complex condition known as transthyretin amyloid cardiomyopathy (ATTR-CM). This condition is believed to affect approximately 50,000-150,000 Americans.
ATTR-CM is a serious and potentially fatal condition, but the diagnosis now comes with a great deal of optimism and hope. The integrated cardiac amyloidosis team at MedStar Heart & Vascular Institute offers advanced, clinically proven therapies to manage symptoms, improve quality of life, and extend longevity for patients with ATTR-CM.
Early diagnosis and advanced treatments now mean more patients than ever can find relief from the symptoms of this complex condition.
Why does ATTR-CM affect multiple organs?
Amyloidosis is a protein misfolding disorder. In this condition, a specific protein in the body malfunctions. It develops an abnormal structure that causes the protein to clump up into insoluble fibers called amyloid fibrils.
These fibrils don’t break down like normal proteins. Instead, they act like cement that builds up inside organs. The specific protein involved in ATTR-CM is called transthyretin (TTR). More than 90% of TTR is produced inside the liver before it travels throughout the body.
Usually, the organs most affected are the heart and the nerves. When amyloid fibrils invade the heart, it’s called ATTR-CM and can lead to serious consequences including heart rhythm problems, low blood pressure, and heart failure.
There are two categories of ATTR-CM depending upon the cause of the condition:
Hereditary (familial or variant disease): This type is caused by a genetic predisposition that is passed down in a family’s genes.
- Wild-type: This is the non-hereditary and most common form. The mechanism of this form of disease remains unknown. Growing older is the most significant risk factor for ATTR-CM. It most often impacts patients over age 60 and becomes more common with age.
What are the symptoms of ATTR-CM?
One of the biggest challenges in diagnosing ATTR-CM is connecting the dots with symptoms that are inconsistent and happening all over the body. Following the clues as a whole, instead of individual symptoms, gives us an opportunity to provide patients relief from this treatable disease.
Classic heart-related symptoms of ATTR-CM include:
Electrical disturbances of the heart causing palpitations or dizziness
- Exercise intolerance, such as stopping a walk to catch your breath
- Fatigue
- Shortness of breath
- Swelling in the legs, feet, and sometimes abdomen (edema)
Other symptoms:
Carpal tunnel syndrome: Tingling in the hands or fingers
- Neuropathy: Tingling, numbness, or burning in the hands and feet
- Orthopedic issues: Spinal stenosis and other problems with the joints
- Popeye’s sign: A ruptured tendon in the arm causes the biceps muscle to bulge, a symptom more common in wild-type ATTR-CM
Related reading: Heart Disease in Women: How Gender-Related Differences Impact a Woman’s Heart.
How is ATTR-CM diagnosed?
The process of diagnosing ATTR-CM is precise, and often non-invasive.
ATTR-CM isn’t the only type of cardiac amyloidosis. During the diagnosis, we first exclude amyloid light chain, or AL. This rare, rapidly progressive, life-threatening condition is an emergency in which the bone marrow produces abnormal cells. We use blood and urine tests to check for AL and treat with chemotherapy if necessary.
We begin our evaluation with an echocardiogram—a non-invasive ultrasound of the heart. We perform blood testing to assess for a signal for AL amyloidosis and for prognostic measures. Other non-invasive scans used to check for amyloid in the heart include:
Technetium pyrophosphate (PYP) scan: This nuclear medicine scan uses radioactive dye to help us see if there is ATTR-CM in the heart.
- Cardiac MRI: A strong magnet and radio waves combine to produce detailed pictures of the heart.
An invasive way to make the diagnosis is a heart biopsy. This outpatient procedure is the most definitive way to make the diagnosis of cardiac amyloidosis.
If you’re diagnosed with ATTR-CM, treatment from experienced specialists can help you regain your quality of life and live longer.
What are the treatments for ATTR-CM?
The U.S. Food and Drug Administration has approved several disease-modifying therapies (DMT) for ATTR-CM. These medications help slow or stop the buildup of amyloid:
Stabilizers: Drugs to steady the TTR protein, preventing it from misfolding and forming amyloid. These drugs include tafamidis (Vyndamax) and acoramidis (Attruby).
- Silencers: These advanced therapies interfere with RNA to reduce the production of TTR protein in the liver. Medications such as vutrisiran (Amvuttra) are given as an injection.
We also work with our patients to treat the consequences of ATTR-CM. Therapies we consider include:
Heart failure treatments: Diuretics help remove excess fluids. Newer drugs called SGLT2 inhibitors such as dapagliflozin (Farxiga) and empagliflozin (Jardiance) have been shown to improve heart failure outcomes for patients with ATTR-CM.
- Rhythm management: As many as 6-7 out of 10 patients with ATTR-CM eventually develop arrhythmias of the heart, such as atrial fibrillation (AFib). These require blood thinners to prevent stroke. Studies show that 10% or more of people with ATTR-CM will need a pacemaker or another device to steady their heart rhythm.
For patients with advanced heart failure, we consider a heart transplant. When other heart failure treatments have been unsuccessful, our experienced specialists and dedicated coordinators work with patients and their families to undergo the transplantation and recovery process.
Related reading: Study Reveals Exciting New Treatment for Cardiac Amyloidosis with Cardiomyopathy.
Does team-based care make a difference for ATTR-CM?
Multidisciplinary care is an essential component of treatment because ATTR-CM is a complex condition that can involve more than one organ.
At MedStar Health, the cardiac amyloidosis program is embedded within our heart failure team. This enables us to take a team-based approach built around our patients and their families. This team includes:
Cardiologists
- Electrophysiologists\
- Genetic counselors
- Neurologists
- Nurse navigators
- Nurse practitioners
- Palliative medicine specialists
This whole-person approach is central to our care model. We provide patients and caregivers with the tools to educate themselves, get support, and address their questions and concerns about ATTR-CM and treatment.
Related reading: Patient-Centered Teamwork: The Power of Multidisciplinary Heart Care.