For years, cardiac amyloidosis was a rare and often fatal disease that had no treatment, so it was not front and center in many cardiology conference sessions or discussions about cardiac imaging. However, that changed in May 2019 with the FDA clearance of the Pfizer drugs Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis), the first pharmaceutical treatments for amyloidosis. This helped lead to an explosion of interest in cardiology to screen for these cardiomyopathy patients so that they could be treated.
In the past four years, amyloidosis has come out of the shadows to the forefront of cardiology education as hospitals and clinics seek more information on how to image and test these patients. This is particularly important because not only is a diagnosis for amyloid needed, but the subtype also needs to be determined.
This was one of the hottest topics at the American Society of Echocardiography (ASE) 2023 annual meeting, where amyloid was the focus of several sessions and mentioned in many others.
Roosha Parikh, MD, an advanced imaging cardiologist with St. Francis Heart Hospital in Long Island, New York, and a clinical assistant professor of medicine at the State University of New York at Stony Brook, presented in one of the ASE 2023 amyloid sessions and spoke with Cardiovascular Business about the disease.
"The first thing people need to know is that it is now treatable, with much better outcomes when treated," she said
Parikh said amyloidosis is often misdiagnosed as other types of cardiac disease because it is not something cardiologists have traditionally looked for in the past. It also has similar symptoms as other types of cardiomyopathies, so it mimics more common diseases.
"It's the great pretender so physicians, and cardiologists especially, do not realize that their patients are showing up with amyloidosis. When they have left ventricular hypertrophy (LVH) and other clinical features, a detailed clinical history is needed and you have to start being suspicious of amyloid," Parikh explained. "You have to think of it, or you will not see it."
She said amyloid is often detected on echo and it is up to the physicians to recognize the signs of the disease and order additional testing such as MRI or nuclear technetium pyrophosphate scintigraphy (Tc99mPYP) SPECT imaging to make a more definitive diagnosis and to gather additional information on the extent of the disease. If there is still suspicion, a cardiac biopsy can be the definitive test.
"It is one of the rare diseases, but the incidence and prevalence of amyloid is not known because people haven't diagnosed it enough. There are some retrospective single-center studies that talk about what the prevalence and incidence is. But now, with people recognizing a lot of the features, advancements in echocardiography and advances in cardiac imaging like PYP scans and MRI, we know so much more now. This is why these patients are getting more scrutiny and getting diagnosed," Parikh said.
Strain echo has become one of the key tools to help diagnosis amyloid. Since strain has become more widely available, now included with most frontline echo systems, it has made diagnosis much easier. Amyloid creates a distinctive pattern on the strain bullseye plot, which has the appearance of a cupcake with a cherry on top, or the cross section of a watermelon.
"Strain is a very important feature, in that if you have that 'cherry on top' bullseye pattern, that should really alert you to look harder for amyloid and go ahead with the next steps," Parikh said.
Multimodality imaging for amyloidosis
One of the next steps is for the patient to undergo more advanced imaging, such as MRI, CT or nuclear imaging.
"There are a lot of things you can see on MRI. You can see the LVH pattern much better, you can see atrial enlargement, you can see thickening of the intra-atrial septum. These are things we can see prettier on MRI than echo, but the big take-home for MRI is the late gadolinium enhancement pattern, the early gadolinium enhancement pattern and being able to look at extra-cellular volume, because amyloidosis in infiltrative of that extra-cellular space," Parikh explained.
In nuclear cardiology a Tc99m-PYP uptake scan can show cardiac amyloidosis. She said this is traditionally used as a bone scan test, but PYP uptake in the myocardium can also be used to calculate the extent of amyloidosis in the tissue.
Mortality rate is high in untreated cardiac amyloidosis patients
Prior to drug treatments, depending on the level of cardiac involvement, she said the median survival was between 2-3 years. But with earlier diagnosis and treatment, this morality rate is improving. She said it is now common in treated patients to have average survival rates of 5 years or more.
Treatment options for cardiac amyloidosis
Parikh said imaging or additional testing needs to differentiate if a patient has the most common primary, or light chain amyloidosis (AL), or amyloidosis transthyretin, also called ATTR cardiomyopathy (ATTR-CM). The treatments for these are different. AL is treated with chemotherapy, monoclonal antibodies, steroids and cyclophosphamide. For ATTR, the new drug tafamidis can be used.
What is amyloidosis?
Amyloidosis is caused by the buildup of abnormal deposits of specific proteins known as amyloid in the body's organs and tissues, interfering with their normal functioning. These protein deposits most frequently occur in the heart and the peripheral nervous system. Heart involvement can result in shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms and death. Involvement of the peripheral nervous system can result in a loss of sensation, pain, or immobility in the arms, legs, hands and feet. Amyloid deposits can also affect the kidneys, eyes, gastrointestinal tract and central nervous system.
Patient history can play an important role, because amyloid often first manifests itself in the seeming unrelated presentation of carpal tunnel syndrome.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com