The Cardiac Amyloidosis Program at Brigham and Women’s

The Cardiac Amyloidosis Program at Brigham and Women’s Hospital was the first of its kind in the United States. Established 10 years ago by Rodney H. Falk, MD, a widely recognized expert in cardiac amyloidosis, the collaborative program has expanded to diagnose and treat every form of amyloidosis, involving experts from cardiology, cardiac pathology, gastroenterology, hematology, nephrology, oncology and neurology.

“The amyloidosis program at Brigham and Women’s Hospital draws on facilities, advanced imaging techniques, and specialized expertise that’s rarely available at other institutions, even major teaching hospitals,” says Dr. Falk.

Diagnosing Cardiac Amyloidosis With Advanced Cardiac Imaging

In recent years, new agents have allowed physicians to treat this previously untreatable disease. In May of 2019, the drug Vyndaqel®(tafamidis meglumine)/Vyndamax™ (tafamidis) became the first FDA-approved drug in the U.S. for transthyretin-mediated amyloidosis involving the heart (ATTR cardiomyopathy). The FDA also recently approved Tegsedi™ (inotersen) and Onpattro® (patisiran), both of which treat familial transthyretin (TTR) amyloidosis with neuropathy.

“We can also diagnose amyloidosis more effectively with the use of technetium pyrophosphate imaging, a nuclear imaging test allows physicians to diagnose cardiac amyloidosis noninvasively, without the need for cardiac biopsy,” says Dr. Falk.

The guidelines for using technetium pyrophosphate nuclear imaging were authored by Sharmila Dorbala, MD, MPH, director of Nuclear Cardiology at the Brigham, and president of the American Society of Nuclear Cardiology (ASNC). Dr. Dorbala also led the development of guidelines to noninvasively diagnose cardiac amyloidosis with imaging techniques, which were published in the Journal of Nuclear Cardiology.

“For the first time, imaging experts conferred with heart failure experts and amyloidosis experts to provide guidance on standardized imaging techniques, diagnostic criteria and appropriate utilization of echocardiography, cardiac MRI and radionuclide imaging in cardiac amyloidosis,” says Dr. Dorbala.

To improve access to cardiovascular care, Sarah Cuddy, M.B.,B.Ch., recently joined the Division of Cardiology at the Brigham to work in the Cardiac Amyloidosis Program. An expert in noninvasive cardiovascular imaging, including cardiac MRI, Dr. Cuddy treats patients with cardiac amyloidosis as well as conducts imaging research at the Brigham.

Identifying Cardiac Amyloidosis Early with Advanced Diagnostic Techniques  

“The major challenge with cardiac amyloidosis is that most patients are diagnosed too late. This makes treatment difficult and less effective. The future of managing this disease will be earlier recognition, so we can start treatment earlier,” says Dr. Falk.

Dr. Falk and his colleagues are developing techniques to effectively identify amyloid in the heart as well as quantify the amount of amyloid. An ongoing NIH-supported project at the Brigham is using PET scanning to evaluate the effects of chemotherapy on the heart in patients with AL amyloidosis. In another study, Brigham investigators are studying the role of gut bacteria in triggering forms of TTR-related amyloidosis.

“Patients with the gene for TTR amyloidosis who have reached an age when the disease commonly occurs—often in the forties and fifties—are referred to Anthony Arnold Amato, MD, who provides a neurologic evaluation and looks for early signs of neurologic disease, while cardiac disease is evaluated in this population by cardiac MRI, echocardiographic and technetium pyrophosphate imaging,” says Dr. Falk.

In 2020, the Partners Biobank will release data for patients who have been found to have genetic risk factors for TTR amyloidosis. Dr. Falk and colleagues are currently developing a program to monitor these patients for early manifestations of the disease.

Treating Amyloid Light-Chain (AL) Amyloidosis Through Collaboration   

Since amyloidosis is a multi-organ disease, Dr. Falk expanded the program beyond the cardiac amyloidosis and now treats every form of the disease.

In AL amyloidosis, amyloid deposits are derived from abnormal immunoglobulins produced by plasm cells in the bone marrow. This form of the amyloidosis can progress rapidly and, if heart failure is present, has a median survival of less than 6 months.

“Since AL amyloidosis progresses so quickly, we see these patients as soon as possible and initiate treatment within a week of evaluation,” says Dr. Falk. “This is done in collaboration with Giada Bianchi MD, the associate director of the amyloidosis program and a member of the Multiple Myeloma Program at the Dana-Farber Cancer Institute.”

Is Cardiac Amyloidosis More Common Than Previously Thought?  

Dr. Falk says the frontier in amyloidosis research and care is recognizing that the disease, particularly TTR amyloidosis, might be more common than currently recognized by most physicians.

“It’s only very recently that doctors have begun to consider how frequently amyloid deposition may contribute to congestive heart failure in the elderly,” says Falk. “The typical form of the disease—a very thick-walled heart leading to heart failure—may only be the tip of the iceberg. While this form of amyloidosis can be easily recognized with echocardiography, there may be many patients who have a much smaller quantities of amyloid deposits, without a specific appearance on echocardiography.”

If an amyloidosis condition does coexist with another cardiac disease, such as hypertensive heart disease, diabetes or ischemic heart disease, it’s possible that the combination of two diseases may produce heart failure where neither alone would have done so.

The recognition of such patients is challenging but may be possible with modern imaging techniques. If so, then current therapies, or drugs currently under investigation, could have an impact on the increasing burden of heart failure in the aging population.

“Whether or not this hypothesis is correct will be proven in the next few years, I think. In the interim, there’s much more to be done for the increasing numbers of patients with AL, TTR and other forms of amyloidosis who we daily treat,” says Dr. Falk.

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