Stanley Cohen saw five cardiologists before doctors finally determined why three years ago he had suddenly begun fainting during his workouts. Two local hospitals in Connecticut disagreed on whether he should have surgery for his enlarged heart muscle, and heart specialists at the Cleveland Clinic initially missed his true diagnosis: a rare condition called cardiac amyloidosis. It’s caused by the accumulation of amyloid plaque — similar to the substance that clogs the brains of Alzheimer’s patients — in his heart.
Finally, the 76-year-old lawyer from Hartford was referred to Brigham and Women’s Hospital in Boston, where Dr. Rodney Falk, one of the top specialists on cardiac amyloidosis in the country, could offer him the best shot at a cure.
Two years ago, Thomas Fiorito, 59, was told to get his affairs in order by his doctors at Emory University Hospital in Atlanta; his amyloidosis was causing severe heart failure that would likely kill him in a few months. Like Cohen, his doctors also misdiagnosed him until his disease was advanced. And Fiorito, too, traveled across state lines to see Falk after his wife found him on an Internet search.
Falk put Cohen on a combination of experimental medications to halt his early heart failure, and that seems to have taken care of the fainting spells. Fiorito underwent a heart transplant because his amyloidosis was more advanced. “I’m doing very well,” he said in a recent interview. “I go swimming, learned how to play golf, and volunteer at a local hospital to counsel heart patients.”
Both he and Cohen credit Falk for saving their lives.
Amyloidosis in the heart is a rare condition affecting an estimated 10,000 Americans. But the true prevalence could be far higher because it is often mistaken for garden-variety heart failure with no known cause.
“It’s potentially a far more common disorder than it appears to be,” especially in African-Americans, who have a 4 percent likelihood of carrying a genetic mutation for the condition, said Falk, director of the Brigham’s Cardiac Amyloidosis Program. Other hereditary mutations have been found in those from Finland, Israel, and Portugal.
Falk estimates that 10 to 15 percent of African-Americans diagnosed with heart failure have signs of amyloidosis — such as abnormally thick heart walls on an imaging test — and should get a genetic test to see if they have the mutation. The test costs $1,000 but is usually covered by insurance.
“It’s a disease that’s potentially treatable,” Falk said, “but if it’s not caught early enough, it will kill you.”
He and the handful of other cardiologists who treat amyloidosis in a few select clinics throughout the country have been trying to spread the word about the condition and the importance of genetic testing in African-Americans.
“We’re trying to raise awareness,” said Dr. Margaret Redfield, a heart failure cardiologist at the Mayo Clinic’s cardiac amyloidosis clinic. She conducted an autopsy study of nearly 100 patients whose cause of death was simply “heart failure” to help get a better sense of the incidence of undiagnosed amyloidosis. The study is currently under review.
One of the patients recently seen at the Mayo Clinic, Maurice Biggs, might have been prevented from facing end-stage heart failure if his doctors in Virginia had considered amyloidosis and performed a genetic test when he showed early signs of heart failure three years ago. The 71-year-old retired Army colonel wasn’t diagnosed with hereditary amyloidosis until this past summer during a routine heart biopsy before a planned surgery. It was too late, however, for him to get a liver transplant to halt production of the amyloid in those with the hereditary form.
“I have a daughter who’s a nurse, and she immediately got the test and she’s negative, so that’s good,” said Biggs, who is African-American. Cardiac amyloid specialists at the Mayo Clinic in Rochester, Minn. — where he was referred by his local doctor —
Amyloid is a misshapen protein that can accumulate in the heart, causing a thickening of the muscle walls and eventually death from heart failure. The abnormal protein is produced in the liver or the bone marrow, but it’s different from beta amyloid, which is involved in Alzheimer’s disease and made from a different abnormal protein. Cardiac amyloid “looks like Jell-O under the microscope,” Falk said. “It makes the heart stiff and damages its function.”
There are three known types of cardiac amyloidosis: senile, which is linked to aging; familial, caused by a hereditary gene mutation; and the worst, light chain, in which amyloid rapidly clogs the liver, kidneys, and nervous system.
“It’s the most devastating form of amyloidosis,” affecting an estimated 3,000 Americans, said Dr. Raymond Comenzo, who specializes in treating light chain amyloidosis at Tufts Medical Center. “About 10 to 15 percent of patients die within three months of diagnosis, no matter what you do.”
Michele Mier of Foxborough was lucky enough to have her light chain amyloidosis diagnosed in the early stages last year before it ravaged her heart or caused progressive, painful paralysis in her limbs. The 65-year-old grandmother had been perfectly healthy, working full time and going to the gym several times a week for years when she became short of breath and suddenly felt her legs become weak, giving out beneath her when she tried to climb stairs.
After her local cardiologist found abnormalities on an echocardiogram, she decided to go to Brigham and Women’s for a fuller workup. A heart biopsy performed by Falk and a bone marrow biopsy performed at Dana-Farber Cancer Institute determined that she not only had extensive amyloid but a blood cancer called multiple myeloma, which occurs 10 to 15 percent of the time in patients with light chain amyloidosis. Several months of chemotherapy administered at Dana-Farber followed by a stem cell transplant last December has put the cancer and amyloidosis into remission.
“I have since retired and am regaining my strength,” Mier said. “When I was diagnosed in July of last year, I asked how long I would live without any treatment and was told probably not past Thanksgiving.”
Perhaps one of the biggest reasons cardiologists aren’t eager to investigate amyloidosis as a cause for heart failure is because it has few effective treatments beyond a heart or liver transplant — or a stem cell transplant in cases of the light chain type.
“There’s currently a race on among pharmaceutical companies to be the first out there with a novel drug for amyloidosis,” said Falk, who treats up to 150 new patients a year. “Once there’s an acceptable treatment, doctors will be thinking about it.” And pharmaceutical companies with proven treatments will be eager to educate them.
Such companies may include Cambridge-based Alnylam Pharmaceuticals, which is currently testing a treatment that targets the gene mutation involved in hereditary amyloidosis to prevent the abnormal protein from forming in the liver.
Researchers from Boston University Medical Center have been testing a non-steroidal anti-inflammatory drug called diflunisal to see whether it can alleviate nerve problems associated with hereditary amyloidosis. They plan on publishing their results in the next few months.
Another promising drug made by Pfizer, called tafamidis, got the thumbs-down from the US Food and Drug Administration last year; the agency asked for more clinical trials to determine whether the drug could effectively halt the paralysis that often makes hereditary amyloidosis, in Falk’s words, “a horrible way to go.”Deborah Kotz can be reached at firstname.lastname@example.org. Follow her on Twitter @debkotz2.