For Physicians Thought Leadership

Ensuring Early and Accurate Diagnosis of Cardiac Amyloidosis to Initiate Timely Multidisciplinary Treatment

This Physician's View opinion piece is written by Marcos Hazday, MD, FACC, cardiologist at the AdventHealth Heart, Lung and Vascular Institute.

Marcos Hazday, MD, FACC
Marcos Hazday, MD, Cardiologist, AdventHealth Heart, Lung and Vascular Institute

Amyloidosis, once thought to be a rare disease, is more common than originally thought. It occurs when amyloid proteins build up in the heart, kidneys, liver, spleen, nervous system or digestive tract, and left untreated, it can result in organ failure. Cardiac amyloidosis, also called amyloid cardiomyopathy, is a form of the disease that can lead to congestive heart failure. In the past, the only available treatment was heart and liver transplant. However, we now have very effective therapies to treat it, especially if the disease is caught early, along with easier ways to diagnose it. Unfortunately, early diagnosis is often missed because cardiac amyloidosis shares many of the same symptoms as hypertensive heart disease and hypertrophic cardiomyopathy. In addition, clinical and echocardiographic findings can mimic aortic stenosis with left ventricular hypertrophy.

AdventHealth recently launched a Center for Amyloidosis to better identify patients with cardiac amyloidosis and provide them with timely treatment. The American College of Cardiology issued an Expert Consensus Decision Pathway earlier this year on providing comprehensive, multidisciplinary care for patients with cardiac amyloidosis, which helped guide development of our new program.

Types of Cardiac Amyloidosis

There are three types of amyloid cardiomyopathy:

  1. Light chain (AL) amyloidosis — Also called primary amyloidosis, it is caused by the accumulation of an immunoglobulin light chain protein produced in bone marrow plasma cell disorders.
  2. Hereditary amyloid transthyretin amyloidosis (ATTRv) — Also called familial transthyretin amyloidosis, this form occurs due to genetic mutations in the transthyretin (TTR) protein (most frequently isoleucine substitution for valine at position 122) and often causes dysfunction in multiple organs and systems, especially the heart and nerves. It is more common among older adults, men and people of African descent. In fact, approximately 3% of African Americans carry this genetic mutation.
  3. Wild-type amyloid transthyretin amyloidosis (ATTRwt) — With this form of the disease, there is no genetic mutation. Instead, the natural TTR protein becomes unstable with age, causing it to misfold and form amyloid deposits, primarily in the heart. It mostly affects those age 75 or older.

Ensuring Accurate Diagnosis of Cardiac Amyloidosis

Some of the most common signs and symptoms of amyloidosis may include the following:

  • Diarrhea, possibly with blood, or constipationcas
  • Enlarged tongue, which might look rippled around the edge
  • Numbness, tingling or pain in the hands or feet
  • Bilateral carpal tunnel syndrome
  • Spinal stenosis
  • Severe fatigue and weakness
  • Shortness of breath
  • Skin changes, such as thickening or easy bruising, and purplish patches around the eyes
  • Swelling of the ankles and legs

Multimodality imaging is required to make an accurate amyloidosis diagnosis. This may include electrocardiography (ECG), echocardiography, cardiac magnetic resonance imaging (CMR) and nuclear imaging. Echo findings indicating amyloidosis can include left ventricular hypertrophy, atrioventricular valve/right ventricular free wall/interatrial septum thickening, diastolic dysfunction, biatrial enlargement and decreased global longitudinal strain with apical sparing. CMR findings may include extracellular volume expansion and diffuse late gadolinium enhancement. However, the gold standard for diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) is a technetium pyrophosphate scan. It is highly accurate and a significant diagnostic advancement that has eliminated the need for invasive cardiac biopsy.

In addition, once an amyloidosis diagnosis is suspected, we conduct a monoclonal protein screen to help determine if the patient has AL amyloidosis, which is a hematological emergency. If AL amyloidosis is ruled out and transthyretin amyloidosis (ATTR) is confirmed, we then conduct genetic testing to differentiate between ATTRv and ATTRwt. For ATTRv cases, our team initiates cascade testing for first-degree relatives.

Treatment Options for ATTR

Determining the specific cause and type of amyloidosis is necessary to identify the proper treatment, and the earlier a patient receives a cardiac amyloidosis diagnosis and starts treatment, the better the outcome. Fortunately, we now have medications that are effective in treating ATTR-CM:

  • In 2019, the U.S. Food and Drug Administration (FDA) approved tafamidis meglumine (VYNDAQEL®) and tafamidis (VYNDAMAXTM) for use in adults with hereditary and wild-type cardiac ATTR. The drug binds with the TTR protein, stabilizing the molecule, and significantly reduces disease progression and mortality.
  • The FDA has also approved two therapies — inotersen and patisiran — for hereditary nerve-involved ATTR (polyneuropathy amyloidosis/ATTRvPN). These pharmacological interventions silence production of the abnormal protein.
  • Diflunisal, a nonsteroidal anti-inflammatory drug, can also stabilize the TTR tetramer.

Finally, researchers are exploring a new CRISPR-Cas9–based therapy called NTLA-2001. Administered by intravenous infusion, it has been designed to reduce TTR after a single dose by editing TTR in hepatocytes, which silences the protein. A Phase I clinical trial is currently underway to test its safety and efficacy in treating ATTRv and ATTRwt.

The Importance of Multidisciplinary Care

Because it is a systemic disorder, amyloidosis can impact more than the heart. The disease can affect the musculoskeletal and neurological systems, causing carpal tunnel syndrome, spinal stenosis and peripheral neuropathy. The gastrointestinal tract may also be impacted, and amyloidosis can lead to renal failure as well. As a result, AdventHealth’s Center for Amyloidosis has assembled a multidisciplinary team that works together to achieve an accurate diagnosis and customize a treatment plan to meet the specific needs of each patient. This team includes the following providers:

Consider Cardiac Amyloidosis as a Diagnosis

We all know that an accurate and timely diagnosis can often save lives, and this is especially true with cardiac amyloidosis. Because the symptoms can mimic those of several other heart conditions, I encourage physicians to consider this alternative diagnosis for any congestive heart failure patient with progressive diastolic dysfunction, even if the initial diagnosis seems clear.

To refer a patient for evaluation by the AdventHealth Center for Amyloidosis, call Call407-303-1648 or complete our patient referral form here.

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