A Look at Cardiac Amyloidosis, a Complex, Underdiagnosed Cause of Heart Problems, with Dr. Stuart Russell and Dr. Kishan Parikh

There are nearly 20,000 proteins present throughout the body, but one protein, in particular, can cause problems when it accumulates in various areas of the body — especially the heart. 

Amyloidosis (am-uh-loi-doh-sis) is a rare disease that occurs when abnormal proteins called amyloid fibrils build up in organs or tissues of the body — leading to dysfunction or damage. While it’s fairly uncommon, many cardiologists believe amyloidosis may not be as rare as it’s considered — but its wide range of seemingly unrelated symptoms can make it difficult to identify and diagnose.

When amyloid fibrils build up in the heart, it’s known as cardiac amyloidosis. Cardiovascular problems that can occur due to amyloidosis include congestive heart failure, rhythm disorders, such as atrial fibrillation and heart valve diseases, including aortic stenosis, among others. Common symptoms caused by these conditions could include the following: 

• Fatigue
• Shortness of breath
• Exercise intolerance
• Heart palpitations
• Fainting or swelling of the lower extremities or abdomen

However, when these proteins build up in other areas of the body, amyloidosis may present in other ways — including carpal tunnel syndrome, enlargement of the tongue, lower back pain caused by spinal stenosis, neuropathy or numbness of the hands and feet, gastrointestinal symptoms, among numerous other health problems. This makes it important to talk to your doctor about any medical symptoms you’re having — even if you don’t think they’re related to the heart.

“While amyloidosis is categorized as rare, what we’re learning is that it’s actually very underrecognized and under-diagnosed — particularly as a common cause of heart failure,” shares Dr. Kishan Parikh, WakeMed Heart & Vascular – Advanced Heart Failure. “Creating more awareness around these conditions can help patients and providers work together to arrive at more timely diagnoses for those with amyloidosis — which can lead to greater quality of life, longevity and overall health.”

Types of Cardiac Amyloidosis

There are numerous types of cardiac amyloidosis — and they are not all created equally. Some are hereditary; while others have no genetic link. 

Here’s a quick overview of the most common types:

Light chain amyloidosis, also known as AL amyloidosis, most often affects people between the ages of 50 and 80 and is more prevalent in males. It’s a bone marrow disorder that occurs when certain proteins (light chain proteins) are misfolded and, therefore, get hung up or accumulate in various organs throughout the body, including the heart.  

Transthyretin amyloidosis, also known as ATTR amyloidosis, is when a protein made by the liver (transthyretin) gets overproduced and, therefore, accumulates in tissues, such as the heart and nerves. There are two subtypes — hereditary ATTR, which is caused by a genetic mutation and may occur in younger adults (ages 50 and up); and wild-type ATTR, which is seen more often in adults age 70 and older. Because ATTR amyloidosis may affect the nerves, it’s sometimes seen with other neurological symptoms, such as carpal tunnel syndrome, lumbar spine problems and difficulty swallowing. It is even associated with bicep tendon ruptures. These non-cardiac symptoms may occur years before any heart-related symptoms occur.

There are several additional rare types of cardiac amyloidosis, including those associated with dialysis, certain blood cancers and more.

How Cardiac Amyloidosis Affects the Heart

The accumulation of proteins can affect both the structure of your heart as well as its ability to pump. 

Here are just a few ways cardiac amyloidosis can impact your heart:

• Thickening of the heart walls and enlargement of the heart occurs when proteins build up in the heart muscle. This makes it harder for the heart to pump, which ultimately leads to heart failure. It’s important to note that patients with heart failure from amyloidosis generally have preserved ejection fraction, which means the heart is pumping properly, but not relaxing as it should.
• Electrical problems occur when the accumulation of proteins disrupts the heart’s normal conduction patterns. This may lead to cardiac arrhythmia or a weakened electrical current. The most common electrical problem associated with amyloidosis is atrial fibrillation.
• Amyloid buildup can cause clusters of protein to form that can stiffen the heart valves — leading to problems such as aortic stenosis.

The wide range of seemingly unrelated symptoms can make cardiac amyloidosis difficult to identify and diagnose.

Diagnosis of Cardiac Amyloidosis

Because this condition presents itself in numerous ways and in various areas of the body, it can be difficult to diagnose.

Dr. Stuart Russell of WakeMed Heart & Vascular – Advanced Heart Failure explains that suspicion of cardiac amyloidosis is the first step to diagnosis. Without suspicion of the disease, doctors wind up simply treating its downstream effects. Unfortunately, in patients with cardiac amyloidosis, standard treatments for heart failure,
rhythm problems and heart valve issues may not be as effective.

“For patients who have ATTR specifically and are experiencing heart failure, standard treatments such as diuretics and blood pressure medications may actually prompt adverse effects — rather than help improve symptoms,” says Dr. Russell. “Likewise, patients who have amyloidosis and a cardiac arrhythmia may not respond to a pacemaker like we’d expect. Those are tell-tale signs that we’re not just treating heart problems, but that there may be another disease process present.”

Once amyloidosis is suspected, the diagnostic path will vary from patient to patient depending on symptoms and medical history. Initial testing may include an ultrasound of the heart (echocardiogram) or an electrocardiogram (ECG) to get a closer look at the cardiac problems. From there, doctors may order an MRI or a biopsy to look for visual or physical evidence of protein buildup. If the genetic form of ATTR is suspected, genetic testing may be required to confirm the diagnosis. Either way, an accurate diagnosis is likely to take time, but is critical to determine the best path to treatment.

“Failure to accurately diagnose and treat cardiac amyloidosis can lead to worsening heart failure and frequent hospitalization — which have a real impact on a patient’s quality of life,” notes Dr. Russell. “The good news is that once we arrive at a diagnosis, there are options for treating it effectively that we didn’t have 10 years ago.”

Depending on the type of amyloidosis and each patient’s symptoms, treatment can vary greatly. Newer medical therapies can be highly effective, particularly the use of medications for ATTR amyloidosis. Other options could include chemotherapy, immunotherapy, or stem cell, liver or kidney transplantation. In most cases, your cardiologist will also treat the specific heart problems caused by amyloidosis, such as heart failure, cardiac arrhythmia or valve problems – using the standard treatment protocols for each of those conditions.

“Cardiac amyloidosis often looks and acts a lot like heart failure — and because it can also lead to heart failure, in many cases it’s not diagnosed until it is more advanced,” explains Dr. Parikh. “If I had to summarize what we want patients to know, it’s this. If you have heart failure, aortic stenosis or a cardiac arrhythmia that’s not responding to traditional treatments — consider asking your cardiologist about amyloidosis.” 

“ The good news is that once we arrive at a diagnosis, there are options for treating it effectively that we didn’t have 10 years ago,” observes Dr. Russell.

This blog is adapted from the summer 2024 edition of Heart to Heart Magazine. Subscribe today.