Cardiac amyloidosis is an uncommon disease, but probably not as rare as many physicians think. It’s part of a series of diseases in which a protein is deposited in various organs, in this particular case in the heart, and these are a variety of proteins. In some cases, the amyloid is derived from abnormal cells in the bone marrow. This is called AL or light-chain amyloid. And it is akin to, very similar to but not identical to, multiple myeloma.
There are other forms of amyloidosis involving the heart. There is a genetic form and it turns out that one in 20 or one in 25 of the African-American population carries a gene, which puts them at risk of developing cardiac amyloidosis later in life. And then there is a form that occurs due to the breakdown of a normal protein, usually in elderly men, men in their seventies. And this refers to amyloidosis of aging. This is a disease which is probably markedly under-diagnosed, and all of these diseases are associated with the development of heart failure, which if untreated is progressive.
The diagnosis of amyloidosis, of cardiac amyloidosis, usually is in the patient who presents with congestive heart failure. Ideally it’s an astute clinician who picks up the echocardiographic abnormalities, maybe moves on to cardiac MRI and suspects the diagnosis.
The symptoms are really those of any patient who has congestive failure: shortness of breath, swelling of the limbs, difficulty lying flat at night. So it’s a very non-specific finding. Once a diagnosis of cardiac amyloidosis has been made, it’s very important to find the precise type. So before treatment we need a biopsy, which can be from outside the heart. In the case of light chain amyloidosis, it is sometimes from taking a small amount of fat from under the skin of the abdomen and examining that with special stains, or it can be with a cardiac biopsy. And then, once the diagnosis has been made and the type of amyloid has been determined, moving into a treatment program with chemotherapy for the light chain amyloid and newer agents for the TTR amyloidosis and screening family members for the familial amyloid patients to make sure that those who are gene positive are diagnosed really early before they develop symptoms.
The program was started here because there was really a need for a center that concentrated on cardiac amyloidosis. Whenever you have a rare disease you need somewhere that sees a lot of patients with that disease so that an expertise can be developed.
The other advantage of having a program for rare disease at the Brigham and Women’s Hospital is that, although it’s a standalone program for the disease, it takes into account the enormous variety and the enormous skills of the physicians here—in cardiology, in the subspecialties as well as the world-renowned experience of the multiple myeloma group at the Dana-Farber Cancer Institute. There are very few places that could offer that, that could come together and treat these complex patients.
Within the next five years the face of amyloid treatment will have changed completely. In the last decade we have seen the mortality decrease dramatically in AL amyloidosis for two reasons. First, because it is being recognized earlier. And second, because the agents initially used for multiple myeloma and pioneered by the Dana-Farber Cancer Institute Myeloma Group, among others, have now become standard therapy and are giving us remission rates that are two to three times what we were obtaining before in cardiac amyloidosis.
I would envisage that if not in five years, then certainly within 10 when we have a patient with TTR amyloid, if the promise of these agents turns out to be true, then we will stabilize their TTR. At the same time we will suppress the TTR. So you’ll knock it down by maybe 80 percent and stabilize the rest and be able to switch off the disease.