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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

University of South Florida study indicates these syndromes, when combined with poor pregnancy outcomes, can confer additional cardiovascular disease risk sooner

Tampa, FL (July 22, 2016) — The short-term risk of  developing cardiovascular disease following a first pregnancy is higher for women experiencing placental syndromes and a preterm birth or an infant born smaller than the usual size, a University of South Florida study reports. The USF researchers also found a five-fold increase in health care costs for women with placental syndromes who developed cardiovascular disease as soon as three to five years following delivery, compared to those who did not.

Their results were recently published online, in advance of print, in the American Journal of Obstetrics and Gynecology. The study, done in collaboration with Baylor College of Medicine, was supported by the Agency for Healthcare Research and Quality.

Dr. Mary Ashley Cain, an assistant professor in the USF Morsani College of Medicine’s Department of Obstetrics and Gynecology, specializes in maternal-fetal medicine.

“Pregnancy does not occur in isolation; it’s part of a woman’s overall health history,” said lead author Mary Ashley Cain, MD, assistant professor in the Department of Obstetrics and Gynecology, USF Health Morsani College of Medicine. “Our study further supports the need for improved interconception care to identify and manage maternal high blood pressure, unhealthy weight and other cardiovascular risk factors before the next pregnancy.”

“Early lifestyle modifications, treatment with appropriate medications and routine follow-up may improve the cardiovascular profile of these patients and help prevent or reduce future poor pregnancy outcomes.”

Other epidemiological studies have shown associations between cardiovascular disease and placental syndromes, including preeclampsia, a condition characterized by high blood pressure in pregnancy; placental infarction, an interruption in blood flow between the placenta and baby; and placental abruption, separation of the placenta from the uterine wall before delivery. However, most previous studies followed women with placental syndrome for long-term risk of adverse cardiovascular outcomes — up to 15 years after giving birth.

The USF study focused on the short-term risk of developing cardiovascular disease — within 5 years of a first pregnancy. Disease arising in this time period would be more likely to affect any future pregnancies. Also, for the first time, researchers evaluated health care utilization and hospital costs to quantify the burden of placental syndrome-associated cardiovascular disease.

The population-based retrospective study followed 302,686 Florida women and girls, ages 15 to 49, with no history of cardiovascular disease before their first documented delivery. Maternal placental syndromes were defined as gestational hypertension, preeclampsia, eclampsia, and placental abruption or infarction. Cardiovascular disease was defined as a diagnosis of coronary heart disease, cerebrovascular disease, peripheral artery disease or congestive heart failure, or a cardiac or peripheral artery revascularization at least 90 days after the delivery discharge date.

Among the USF researchers’ findings:

• After adjusting for sociodemographic, clinical and behavioral factors, women with any placental syndrome had a 19-percent higher risk of developing cardiovascular disease within five years of their first pregnancy than women without PS.
• When placental syndrome was combined with poor fetal outcomes – either preterm birth or small for gestational age, or both – the risk of cardiovascular disease upon short-term follow-up increased to 45 percent.
• Women with placental syndromes who subsequently developed cardiovascular disease incurred a five-fold increase in health care-related costs during short-term follow-up, compared to those who did not develop cardiovascular disease.
• The researchers concluded that preventing placental syndromes in the 36,713 women with one or more placental syndromes in their study population would have “saved more than $63 million in direct costs of inpatient and emergency care during the average 5-year follow-up period.”

Dr. Cain led the population-based retrospective study on maternal placental syndromes and short-term cardiovascular outcomes.

Just how hypertensive disorders of pregnancy and related placental abnormalities may increase premature cardiovascular disease risk in women with no apparent medical history of heart disease requires more research.

“It’s a chicken-or-the-egg situation,” Dr. Cain says. “We don’t know whether existing (asymptomatic) baseline cardiovascular disease is unmasked by placental syndromes in some pregnant woman, or if something about the placental syndromes triggers damage to mothers’ blood vessels that can lead to cardiovascular disease.”

Dr. Cain, who specializes in maternal-fetal medicine, is working with Aarti Patel, MD, assistant professor of cardiology at USF Health, to create a postpartum follow-up clinic for women with increased risk of cardiovascular disease. Patients will be seen at both the USF Health South Tampa Center for Advanced Healthcare and Tampa General Hospital’s Genesis Center and include those who have experienced placental syndromes and/or adverse pregnancy outcomes.

Article citation:
Mary Ashley Cain, MD; Jason L. Salemi, PhD; Jean Paul Tanner, MPH; Russell S. Kirby, PhD; Hamisu M. Salihu, MD, PhD; and Judette M. Louis, MD, MPH; “Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes,” American Journal of Obstetrics & Gynecology, 2016 Jun 2. pii: S0002-9378(16)30267-8. doi: 10.1016/j.ajog.2016.05.047. [Epub ahead of print].

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USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu

Media contact:
Anne DeLotto Baier, USF Health Communications
abaier@health.usf.edu or (813) 974-3303

Photos by Eric Younghans, USF Health Communications & Marketing