Pat and Jim Calhoun Cardiology Center

Making the Connection

By Stacey Mancarella

Illustrations by Yesenia Carrero

illustration of photos of unconnected symptoms

A rare but debilitating condition, hereditary amyloidosis (hATTR) presents as seemingly unrelated illnesses that mask the root cause. But increased awareness and new treatment options bring hope for sufferers of this devastating genetic condition.


We hear of it too often in health care. Even with the most diligent doctors and patients, sometimes figuring out the correct diagnosis of a rare medical condition can be a challenge.

Unexplained weight loss and diarrhea. Shortness of breath during exercise. Carpal tunnel syndrome. Weakness and difficulty balancing that gets progressively worse. Tingling or numbness in the hands and feet. Symptoms like these point to different culprits, bringing patients to a variety of specialists and glimmers of hope as they find potential answers. But treating one symptom doesn’t help the others, and everything gets worse.

This particular collection of ailments, among other symptoms, points to hereditary amyloidosis (hATTR), a devastating genetic disease that, up until recently, was considered untreatable. Dr. Fernanda Wajnsztajn is all too familiar with the plight of her patients who have searched in vain for a diagnosis. A neurologist at the UConn Health neuropathy clinic, Wajnsztajn specializes in peripheral neuropathy, damage or disease of the peripheral nervous system.

“Because some of the symptoms of hereditary amyloidosis are also seen in a variety of diseases, some of my patients went to several doctors for years until hATTR was suspected,” she says. “With a detailed history, we are also able to trace the heritage of patients, and, often, patients realize during the interview that some their relatives also have similar symptoms.”

Now these families have options. New drug treatments have been approved to treat neuropathy, the nerve pain, tingling, or numbness that’s a symptom of this little-known disease, and doctors at UConn Health have assembled a team to tackle hATTR head on.

Interpreting the Evidence

Wajnsztajn has been aware of hATTR since her days at Columbia University, where she was involved in research and clinical trials for hATTR therapies. Only about 50,000 people worldwide are affected by hATTR, “but we suspect that many cases go undiagnosed or misdiagnosed,” Wajnzsztajn says. “Our goal is to reach those people.”

Hereditary amyloidosis is caused by a hereditary mutation of the TTR gene. If one parent carries the gene mutation, offspring have a 50 percent chance of inheriting the disease. Hereditary amyloidosis wreaks havoc on the body by depositing amyloid proteins into organs, most commonly the heart, nerves, and digestive tract. These deposits cause the organs to function improperly, which eventually leads to a myriad of debilitating symptoms.

Even though the gene mutation is present at birth, most patients don’t experience symptoms until well into adulthood. And even once symptoms start, it can take years for a proper diagnosis.

“Hereditary amyloidosis is not a well-known disease. The patient can present with a history of heart problems and receive a diagnosis of polyneuropathy, but if the doctor isn’t familiar with it, they won’t put it together. It’s easy to miss,” Wajnsztajn says.

For example, two of the most common symptoms of hereditary amyloidosis are carpal tunnel and cardiomyopathy, or heart muscle disease. Because these two diseases are seemingly unrelated and treated by different kinds of doctors, hereditary amyloidosis can go undetected. The average delay in diagnosis is four years, and in that time, amyloid is continuously deposited into the affected organs, causing symptoms to worsen.

Even with the new treatments, a timely diagnosis is important as the medications cannot reverse the symptoms but only prevent further protein deposits that cause the condition to worsen. The earlier a patient can be identified and a course of treatment initiated, the slower the disease will progress.

Dr. Fernanda Wajnzsztajn (left) and Dr. Sarah Tabtabai discuss a patient case.

Dr. Fernanda Wajnsztajn (left) and Dr. Sarah Tabtabai discuss a patient case.

Case Closed

UConn Health’s multidisciplinary approach can shorten this delay, giving patients relief sooner and stopping hATTR in its tracks. Cardiologists at the Pat and Jim Calhoun Cardiology Center work hand in hand with neurologists from the peripheral nerve disease clinic to examine a patient’s symptoms, get that crucial neuropathy or polyneuropathy diagnosis, and schedule them for genetic testing to confirm a hATTR diagnosis. Once the diagnosis is confirmed, treatment can begin very quickly, and the deposition of amyloid into the organs is halted within weeks — sometimes within days — thanks to neurologists, cardiologists, neuropathy testing, and an infusion center to administer treatment being all in one place.

Two treatment options currently exist, one that’s infused intravenously every three weeks, the other given by weekly subcutaneous injection. These new treatments work by inhibiting the body’s ability to create the amyloid protein. They reduce the amount of the protein the liver can make by 84 percent, improving the patient’s quality of life. Clinical trials are ongoing, with the hope that such medications can treat other types of amyloidosis as well.

“Before medicines like this came along, there was really no therapy for this particular heart disease. It’s progressive and very debilitating, and the hereditary type, in particular, occurs in younger people,” says Dr. Sarah Tabtabai, cardiologist at the Pat and Jim Calhoun Cardiology Center at UConn Health.

Previously attempted treatments for hATTR symptoms were drastic, sometimes including heart transplants or heart and liver transplants, Tabtabai says. But with the new medications, “patients have had good outcomes with both their neurologic disease and their heart disease, and it sort of keeps things at bay.”

Close collaboration between the departments makes everything go smoothly for patients who have already waited so long for answers, says Wajnsztajn.

“We work very closely with cardiology to obtain the appropriate exams for diagnosis as quickly as possible. Despite being a challenging or daunting diagnosis, our patients feel fortunate that they finally have answers, and we are able to provide the most advanced treatments along with the support necessary,” she says.

Because of the high rate of misdiagnosis, the companies that produce the new medications are currently offering free screenings for patients with suspected hereditary amyloidosis. A patient simply has to schedule the genetic test at UConn Health, and the billing is handled directly through the hospital, creating a streamlined process for the patient.

Early diagnosis of hATTR can also bring awareness to family members who might be afflicted.

“Once a patient is diagnosed with hereditary amyloidosis, we can test blood relatives as well to identify any members of their family who may also have this disease,” Tabtabai says. “The hope is that, down the line, we can offer medications like this sooner, before patients become symptomatic or right at the onset of symptoms so that they fare even better as time goes on.”

Helping Patients with Internet Gaming Addiction

Q&A with Nancy Petry, Ph.D., internet addiction expert

Q

How prominent is internet addiction in the U.S.?

The explosion of our use of the internet, computers, and mobile technology is fairly new, so no one really knows the prevalence of internet or screen addiction as it hasn’t been studied nor standardly assessed. But the NIH took a significant step to begin funding my research in this area, so there soon will be insights. In December 2017, the World Health Organization announced it would be recognizing “gaming disorder” as a mental health condition in its 11th International Classification of Diseases.


Q

Who is at most risk of a gaming disorder?

Anyone, regardless of age or gender, who plays video or online games excessively may be at risk of becoming addicted. However, the most vulnerable population may be the more than 90 percent of boys ages 8 to 17 who play. While the lives of the vast majority of child gamers are not adversely impacted, about 1.5 percent of children develop significant problems when they begin to play for very long hours and forego other activities to play games. Children with a video game addiction play 3 to 8 hours daily, sometimes more.

Boys are at much greater risk than girls because they play electronic games more. Children who are more socially isolated, or have depression or attention deficit disorder (ADD) are also at greater risk. Parents should be aware of warning signs including new problems at school, trouble with or a decline in social interactions with family and friends, and a reduction in other hobbies they once enjoyed.


Q

Tell us about your novel video gaming disorder research study aiming to curb the problem.

We at UConn Health have the first NIH-funded clinical trial to help parents with their child’s video game addiction. The study tests the benefits of a family therapy approach, with one or both parents and the child participating. The children are ages 10-19 and they must have developed significant problems related to gaming. Parents are coached on how to better understand what gaming addiction is, why their child derives pleasure from the activity, and the best ways to monitor and intervene to reduce their child’s gaming. There are no other such studies in the U.S. to our knowledge, and only a handful of studies in Europe and Southeast Asia have evaluated interventions.


Q

What do you recommend to patients to curb Internet or gaming use?

Electronics are a big part of daily life, and they are not going away. It is up to each of us to limit internet or game use and make sure we, and our children, are not losing out on other things in life due to excessive use. Just like everything else, moderation is key. If you notice you or a loved one has or may become addicted to the internet or gaming, set rules such as no gaming or electronics use after 9 p.m. and start to make time for other hobbies you enjoy.

Protecting Cancer Patients’ Heart Health

Kim Agnes looks at heart

Dr. Agnes Kim, director of the Cardio-Oncology Program at UConn Health, uses new echocardiography strain imaging to detect signs of potential heart problems in cancer patients, before clinical symptoms are evident.


There are currently more than 15 million cancer survivors in the U.S., and that number is expected to grow to 20 million within 10 years. But as more patients survive cancer, the risk of developing cardiovascular health issues from lifesaving chemotherapy and radiation treatments also is increasing.

In an effort to detect cardiac health risks or conditions early, UConn Health has begun tracking cancer patients with an advanced heart imaging test before, during, and after chemotherapy and radiation therapy.

New echocardiography strain imaging allows cardiologists to hunt for early warning signs of heart muscle function changes or damage within the heart tissue. The in-depth strain analysis is powered by traditional ultrasound technology, which uses high-frequency soundwaves to create a sonogram of the pumping heart.

Dr. Agnes Kim, director of the Cardio-Oncology Program at the Pat and Jim Calhoun Cardiology Center at UConn Health, says it’s very important to monitor cancer patients for any signs of cardiac toxicity.

“Echo strain imaging has been compared to a canary in a coal mine,” she says. “We are so grateful that our cancer patients have access to this latest technology so that we can monitor and intervene early if any warning signs are present.”

Studies have shown that confirming any changes in heart muscle strain can help doctors predict whether a patient is at risk for cardiotoxicity and its side effect of future heart failure. A decline in heart strain of 15 percent or more suggests cardiotoxicity, and doctors may prescribe cardio-protective drugs, such as beta-blockers or ACE inhibitors, or modify the patient’s chemotherapy dosage.

Possible cardiotoxicity side effects from chemotherapy medications include a lowering of overall heart muscle function, which can lead to heart failure, formation of blood clots, or an increase in blood pressure. The side effects of radiation therapy also can lead to damaged heart muscle, heart valves, and arteries, or impact the lining of the heart.

Kim launched the Cardio-Oncology Program in 2014 to ensure UConn Health had an integrated program of oncologists and cardiologists, allowing for coordinated care to address the potential risks to heart health that can arise from cancer treatment.

The program also is studying the presence of serum biomarkers in the blood for predicting whether a cancer patient is at high risk for cardiotoxicity, as well as tracking cancer patients’ long-term heart health to analyze the impact of additional clinical care protections.

Fitbit Helps Save Patient’s Life

UConn Doctor checks patient's heart


This January, Patricia Lauder of Harwinton, Connecticut, had an illness she just couldn’t shake. Visits to doctors, testing, and X-rays came back negative for pneumonia or any other health issues.

Lauder started experiencing shortness of breath and fatigue after walking short distances. She noticed that her Fitbit fitness tracker — which the 73-year-old purchased after retiring to help her get in shape — was showing her resting heart rate increasing by five points a day.

On the day her resting heart rate spiked to 140 beats per minute, she called an ambulance.

A CT scan at UConn John Dempsey Hospital revealed she was suffering from two large blood clots in her lung arteries, known as pulmonary embolisms.

According to Dr. JuYong Lee, director of vascular and endovascular medicine at UConn Health’s Pat and Jim Calhoun Cardiology Center, the mortality rate of a pulmonary embolism is more than 30 percent when it is massive.

Lee decided to intervene right away with an innovative, minimally invasive solution, applying clot-blusting drugs directly into the clots through a catheter.

The next day, Lauder’s blood clots were gone and her lung and heart health totally normalized.

“If I didn’t have a Fitbit on my wrist, I might not be here to tell my story,” Lauder says.