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Can Abnormal Liver Proteins Cause Heart Failure?

Neuropathy, sudden weight loss, carpal tunnel and fainting led to a patient’s 20-year journey to an accurate diagnosis of cardiac amyloidosis.

Few patients look forward to doctor visits – least of all Marianne Foley-McGuire.

For the first 20 years of her life, Marianne had to undergo annual plastic surgery of a cleft palate. As a result, she says, “By the time I was 21, I really wasn’t into going to the doctor for anything. Those yearly surgeries motivated me to take care of myself, except for one annual checkup by my family doctor and one by my gynecologist. Otherwise, I exercised, tried to eat well, and for years, I never had any medical issues.”

That changed when Marianne reached her early 40s. She had to have carpal tunnel surgery in both of her wrists, and rotator cuff surgery in both of her shoulder blades. Her legs began feeling numb below the knees and felt chapped, even though there was no actual chapping.

By the time she was in her 50s, Marianne was experiencing periodic fainting spells and appetite loss that eventually led her to lose 70 pounds.  In her final years as a high school teacher before taking early retirement, she couldn’t put herself through the ordeal of climbing the steps to her classroom more than once a day – “My legs felt like they had bricks tied to the ankles,” she recalls – and had to eat her lunch there rather than downstairs in the cafeteria.

Particularly frustrating for Marianne was her limited ability to sightsee, dine and take cooking classes during trips she took with her husband to Italy and Spain.

“It turns out that all of my problems were symptoms of cardiac amyloidosis,” says Marianne.  “But for years, I had no idea that I had this illness, and neither did my family doctor and gynecologist, who wrote my symptoms off to aging.”

Amyloidosis Diagnosis

It’s not entirely surprising that Marianne’s illness was not identified sooner, according to cardiologist Dr. Yevgeniy Brailovsky, who currently co-leads Marianne’s multidisciplinary care team with neurologist Dr. Hristelina S. Ilieva.

“This type of journey, unfortunately, is not uncommon for patients who are eventually diagnosed with amyloidosis,” says Dr. Brailovsky. “Its symptoms, including syncope, or fainting, neuropathy, unexplained weight loss and carpal tunnel syndrome requiring surgery, are common and non-specific by themselves. Taken together, however, they may suggest this under-recognized systemic disease.”

Finally, at the insistence of her husband, a pharmaceuticals researcher, and various other relatives who were also healthcare professionals, Marianne began seeing a team of Jefferson physicians. In March 2020, one of these specialists, neurologist Dr. Lori A. Sheehan, eliminated Parkinson’s disease and multiple sclerosis as possible diagnoses and referred Marianne to cardiologist Dr. Paulina Gorodin-Kiliddar of Jefferson’s Women’s Primary & Specialty Care.

Marianne credits Dr. Sheehan as the first physician to take her symptoms seriously, and Dr. Gorodin-Kiliddar as the first to suspect that hereditary ATTR (hATTR) amyloidosis might be the cause of them. After examining Marianne’s EKG and prescribing midodrine to ease her fainting, Dr. Gorodin-Kiliddar had Marianne take a genealogy test and sent her to a heart failure specialist, who had her undergo a cardiac PYP scan. This test uses a radioactive form of the chemical compound pyrophosphate (PYP) to detect cardiac amyloidosis. The genealogy results and cardiac PYP scan revealed that Marianne’s liver was producing abnormal proteins that were accumulating in her heart, confirming Dr. Gorodin-Kiliddar’s diagnosis of cardiac amyloidosis.

Amyloidosis Basics

There are various types of amyloidosis, depending on the main underlying protein abnormality. Two broad categories are amyloid light chain (AL) and amyloid transthyretin (ATTR). AL is a blood-related cancer that occurs when plasma cells start to grow uncontrollably and produce antibody components that come together, change shape and form amyloid fibrils, which deposit in different tissues and lead to organs not working properly.

ATTR is caused by an abnormal amount of misfolded transthyretin protein in organs and tissues. It is sometimes hereditary. Marianne, who is of Irish descent, was diagnosed with hereditary-type transthyretin cardiac amyloidosis (hATTR-CM).  Abnormal proteins in her liver were clogging up her heart, so that she was developing heart failure, as her father had had.

“Thanks to research on this topic, we know that although hATTR amyloidosis is present all over the world, Ireland is a cluster spot,” says Dr. Ilieva. “Among others are Portugal and Brazil. Another type of mutation of the hATTR gene is carried by 3.5 to 4% of the African American population. Not all family members inherit the gene, and gaps in family medical knowledge may obscure the fact that there is an inherited condition.”

Polyneuropathy

In July 2020, Dr. Ilieva expanded Marianne’s diagnosis to include amyloid polyneuropathy (hATTR-PN).

“It was notable that Marianne’s bilateral carpal tunnel syndrome was worse on her non-dominant left hand than on her right,” says Dr. Ilieva. “Another red flag was that despite having surgeries, she continued to have tingling sensations in both hands. One more notable aspect of her presentation is that she had developed autonomic neuropathy. This sort of neuropathy affects the nerves that are part of the autonomic functions of our body, like maintaining normal blood pressure in different body positions and normal function of the GI tract. That’s why Marianne experienced episodes of dizziness and lightheadedness and lost weight.”

Breakthrough Medications, Relief and Optimism

But fortunately, as Dr. Brailovsky notes, “There is new research showing several medications that are specifically approved for the treatment of amyloidosis affecting the heart and the nervous system. These medications require expertise in neurology and cardiology for careful patient assessment and follow-up to ensure successful treatment.”

In September, Dr. Brailovsky and Dr. Ilieva told Marianne about a new treatment breakthrough, patisiran, which is an infusion medication that helps ease the neuropathy in her legs so she can walk better. Since then, Marianne has been receiving patisiran infusions for five hours once every three weeks at Jefferson. By spring, according to Dr. Brailovsky, she may be able to begin injections of vutrisiran, currently an investigational agent given subcutaneously every three months, instead of the time-consuming infusions. Once a day, Marianne also takes tafamidis, an oral medication that can help patients with ATTR-CM live longer with fewer heart-related hospital visits.

Since beginning these treatments several months ago, Marianne has been feeling better, gained back about 15 pounds, and is feeling hopeful.

“I feel very well taken care of at Jefferson,” says Marianne, “and optimistic that medical science will continue to make breakthroughs in dealing with amyloidosis. Dr. Brailovsky, Dr. Ilieva and the team of nurses at the Jefferson Infusion Center are truly what it means to be healthcare professionals; they go above and beyond their roles in making me feel respected and cared for as a patient with a rare disease.”

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