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USF Health has established a Neurocardiogenetics Clinic focused on improving the quality of life for patients with hereditary neuromuscular disorders who are at risk for or already experiencing cardiac complications. Innovative genetic research is a central component of the new clinic.

The multidisciplinary clinic teams faculty and staff with clinical expertise in cardiology, genetics and neurology. The clinic is directed by Aarti Patel, MD, assistant professor of cardiology and director of the Cardiac Imaging Fellowship Program at USF Health in collaboration with Thomas McDonald, MD, professor of cardiology and molecular pharmacology and physiology, and a member of the USF Health Heart Institute, and Theresa Zesiewicz, MD, professor of neurology and director of the USF Health Ataxia Research Center. Patients receive a complete cardiac examination and testing along with a comprehensive family genetic evaluation from providers familiar with their neurological history.

“Combining all that information, we are able to come up with a personalized treatment plan,” Dr. Patel said.

Many patients initially seen at the Neurocardiogenetics Clinic have been diagnosed with Friedreich’s ataxia (FA), a rare, debilitating and life-shortening neuromuscular disorder that usually strikes in childhood. At some point in their lives 55 to 60-percent of FA patients develop some form of cardiac disease. The most devastating of these is cardiomyopathy, a heart muscle disease that limits blood pumped to the rest of the body and increases risk for heart failure and abnormal heart rhythms.

“FA is a multisystem disease that affects many different parts of the body, including the heart,” Dr. Zesiewicz said. “And one of its most sinister complications is cardiomyopathy, an enlarged heart.”

The Neurocardiogenetic clinic offers patients and their families the opportunity to participate in ongoing genetic studies exploring potential links between heart disease and neuromuscular diseases like FA and certain types of other ataxias and muscular dystrophies.

Dr. Aarti Patel (left), assistant professor of cardiology, collaborates with Dr. Thomas McDonald, professor of molecular pharmacology and physiology, at the new USF Health Neurocardiogenetics Clinic. Dr. Theresa Zesiewicz. professor of neurology (not pictured), is another collaborator.

While a deficiency in the frataxin protein can lead to fibrosis and scarring of heart muscle tissue in FA, competing theories exist about how a genetic mutation may actually result in heart problems in this particular ataxia and other neuromuscular disorders.

Dr. McDonald’s research team is searching for answers to many questions, including how different genetic variations may lead to cardiac abnormalities and affect the severity of heart disease.

Small blood samples are collected from patient volunteers with different inherited neuromuscular and/or cardiac disorders, as well as family members who are unaffected genetic carriers of neuromuscular diseases. In laboratory cell culture dishes, USF Health researchers genetically reprogram the blood cells into pluripotent stem cells that can grow into any cell type. Then they induce these stem cells — containing the same genetic make-up as the patient who provided blood — to become nerve cells and heart muscle cells.

The goal is to work out at a molecular level how FA or other inherited neuromuscular diseases damage the heart muscle. Once that is achieved, Dr. McDonald said, the “disease in a dish” can be used to identify potential drug targets and test treatment options on the patient’s own cells.

“With stem cell technology and disease-in-a-dish modeling, we’re looking for the earliest changes in either a heart or a nerve cell (that lead to disease),” he said. “A big unanswered question is whether the molecular or cellular process happening in the nerve is the same as that damaging the heart muscle. By using stem cell-based research we hope to be able to determine if there is a connection between the nerve and the heart – or whether it’s a separate, independent process but based upon the same genetic defect.”

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The collaborative research builds upon robust data collected by doctors in the clinic, including the wide range of symptoms seen in patients with hereditary neurological disorders involving cardiac complications.

Ultimately, that can help improve understanding of why genetic variations in certain neuromuscular diseases cause cardiac complications, Dr. McDonald said. “Having a clear clinical picture of each research participant will help us correlate the genetics and function of cells we see in the laboratory with how that translates to disease progression in the individual.”

“With careful clinical surveillance and novel biomarkers, our hope is that we will be able to predict which patients and their family members are at highest risk for cardiovascular disease so we can intervene early with effective treatment,” Dr. Patel said. “We’re hoping to identify patients even before they develop cardiac symptoms, so we can prevent heart disease.”

-Video and photos by Allison Long, USF Health Communications and Marketing

Michael Fradley, MD, had finished medical school. He’d completed training in internal medicine and cardiology.   He decided to pursue further training in electrophysiology, and began observing a substantial number of cancer patients were experiencing abnormal heart rhythms.   Then, in the midst of his fellowship, the unthinkable happened.  He received his own cancer diagnosis – melanoma.

“I had to undergo certain procedures and treatments but fortunately now I’m fine,” said Dr. Fradley, associate professor of medicine at the USF Health Morsani College of Medicine.  “As a result of this experience, I had this very new perspective on my life and my career. I had been personally affected by cancer … and I have this passion for cardiology. Wouldn’t it be an amazing opportunity to try to bring the two together?”

USF Health cardiologist Michael Fradley, MD, speaks to a patient at the Cardio-Oncology Clinic at Moffitt Cancer Center.

While Dr. Fradley was finishing his electrophysiology fellowship, Roohi Ismail-Khan, MD, a medical oncologist at Moffitt Cancer Center, was noticing a worrying trend — many of her breast cancer patients experienced cardiac issues during and after treatment. “We were getting much better at treating cancer,” she said, but “why put patients through something that’s going to help them survive the cancer and then have [cardiac] issues to deal with later on?” So, in late 2014, about a year after Dr. Fradley joined the cardiology team at USF Health, the pair began a Cardio-Oncology Program jointly developed by USF Health and Moffitt. “It was all just a perfect fit,” Dr. Fradley said.

Integrating research into cardio-oncology care

Cardio-oncology is an emerging field — one in which there are still many questions left to answer. Dr. Fradley and Dr. Ismail-Kahn didn’t just want to treat patients; they wanted to research how to do it better. They enlisted the help of biomedical engineer Hua Pan, PhD, MBA, an assistant professor of cardiovascular sciences and member of the USF Health Heart Institute. Dr. Pan conducts basic and translational research on the molecular mechanisms through which cancer treatments damage the heart. This includes investigating genetic signals that may help predict which patients receiving new drugs to boost the body’s immune system response against certain cancers are likely to develop cardiovascular complications.

Biomedical engineer Hua Pan, PhD, a member of the USF Health Heart Institute, works with Dr. Fradley and collaborators at Moffitt Cancer Center to incorporate basic science and translational research into the joint Cardio-Oncology Program.

The cardiologist, oncologist and basic scientist came together to form a powerful academic research and training program. “It’s one of the first [cardio-oncology programs] in this nation to incorporate basic science and the translational component into a cardio-oncology program,” Dr. Pan said. “It connected the dots. This is very unique.”

There was a time when a cancer diagnosis was almost equivalent to a death sentence. Nowadays, nearly 70% of people diagnosed with cancer will survive, thanks to the advent of treatments like chemotherapy, radiation therapy, and immunotherapy, according to the National Cancer Institute. But those life-saving therapies have come at a cost. Up to 30% of cancer patients develop cardiovascular complications. The issue is so common that it’s become the leading cause of death in cancer survivors. Those therapies, which so effectively attack cancer cells, can also damage the heart and increase the risk of heart disease in the future. And if a patient is already at risk of heart disease due to obesity, diabetes, or genetics, that risk is amplified by cancer treatment.

A collaboration that optimizes treatment

That’s something Dr. Ismail-Kahn had to consider when treating patients. For patients with clear risk factors for heart disease, she might choose a less aggressive — and potentially less effective — treatment plan to avoid cardiac complications.

Now, when a patient comes to see Dr. Ismail-Kahn for cancer treatment, she sets the patient up with an appointment with Dr. Fradley as well. Dr. Ismail-Kahn determines the ideal treatment for the patient’s cancer. She’ll send that information to Dr. Fradley, who after reviewing the patient’s cardiac history and conducting various tests on the patient’s heart and blood, will develop a plan to monitor and prevent cardiovascular complications throughout treatment. That plan may require guiding the patient through preventive measures like changes in diet and exercise or starting the patient on cardiac medications. It will also include regular cardiac checkups with Dr. Fradley so he can identify any cardiac effects before they become severe and offer an intervention or suggest a temporary break from cancer treatment if needed.

Moffitt Cancer Center oncologist Roohi Ismail-Khan, MD

“Let’s just say I have an 80-year-old patient with history of heart disease and she needs certain chemotherapy and certain targeted therapy to help with her cancer,” Dr. Ismail-Kahn said. Before working with a cardio-oncologist, she might have chosen a less effective treatment plan in order to prevent heart disease. Now, she says she’s “braver in treating patients.” Working with a cardio-oncologist who understands how cancer drugs interact with the heart, can watch the heart closely, and knows what interventions can help, gives her confidence that any cardiovascular risks will be managed appropriately so that she can give the right treatment for each patient.

One of the nation’s first cardio-oncology fellowships

But there aren’t enough cardio-oncologists for all programs to offer such care. As such, Dr. Fradley developed one of the first cardio-oncology fellowship programs in the United States, focusing on training a new generation of cardiologists to specialize in this field. ‘It’s important for trainees to get dedicated exposure to the complexities of this patient population,” Dr. Fradley explained. “This is an excellent opportunity to disseminate knowledge to other institutions and organizations. And these individuals will become the future leaders of the specialty.”

Moving the field forward will take more than training new specialists. That’s why the program is set up to conduct multidisciplinary research while it offers its multidisciplinary treatment. The physicians treating patients every day see first-hand which questions need to be answered to improve care. Not only do they design studies to test clinical interventions, but they pass their questions along to Dr. Pan through a special communication channel designed by Dr. Fradley to facilitate conversations between the extremely busy team members. Dr. Pan can use their observations to guide her studies looking at what patients are experiencing on a molecular level. This understanding can then be used to develop better, more precise treatments.

“A combination of both clinical investigation and translational research is necessary to advance the field,” Dr. Fradley said.

Cancer survivor Abby Jones with her husband Ross on a recent vacation in Colorado. Jones, one of the first patients in the Cardio-Oncology Program jointly developed by USF Health and Moffitt Cancer Center, credits the program with playing a “huge part” in helping restore her health.

Heart healthy and cancer free

The future of cardio-oncology is exciting, but the program is already making a huge difference for patients in Florida, like Abby Jones of Ocala.  Jones was one of the very first patients to participate in the program for cancers of her lung and kidney (removed completely by surgery) and breast cancer. She was young and otherwise healthy, so Dr. Ismail-Khan decided to treat Jones’ bilateral breast cancer with the most aggressive therapy available.  During chemotherapy and targeted therapy with the drug trastuzumab (a combination with a high likelihood of cure, but that can have toxic effects on the heart), Jones received routine echocardiograms to monitor her cardiac function.  When one of echocardiograms revealed that her heart wasn’t pumping effectively, Dr. Ismail-Khan immediately referred Jones to Dr. Fradley in the Cardio-Oncology Clinic.

Dr. Fradley recommended a 7-week break from the chemotherapy, during which Jones took low-dose blood pressure medications. Soon, she was able to safely continue her chemotherapy. Today, she is cancer-free. (In fall 2016, a different type of breast cancer was detected early; Jones underwent a lumpectomy, her heart was closely monitored during another potentially cardiotoxic chemotherapy regimen, and the treatment succeeded without cardiac complications.)

Jones continues annual appointments with Dr. Fradley to ensure her heart remains healthy, and follows up with Dr. Ismail-Khan to make sure she remains cancer-free.

“I’m two years clean from the most recent diagnosis and celebrating life. The Cardio-Oncology team played a huge part in helping me get back to myself,” she said. “We welcomed newborn twins into our home as foster children earlier this year with a goal of adoption on the horizon.  And last month, I got to drop my oldest off at his first day of kindergarten… it was so fun to watch!”

Jones with Dr. Fradley and Dr. Ismail-Khan at a luncheon in February 2016, marking the first year of the newly established Cardio-Oncology Program.

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Moffitt Cancer Center and USF Health (with Drs. Fradley and Ismail-Khan as co-chairs) will host the fourth Cardio-Oncology Summit, Sept. 27 and 28, at the Hilton Tampa Downtown, alongside the International Cardio-Oncology Society, the Canadian Cardiac Oncology Network and the British Cardio-Oncology Society.  This is the summit’s first time in Tampa; previous conferences have been held in London, Vancouver and Nashville. More than 320 participants from 23 countries are expected to attend the summit, which models a leading-edge interdisciplinary approach to preventive and targeted medicine in cardio-oncology. Read more.

-Story by Emma Yasinski