Research at University of Oklahoma, VA Medical Center and Vanderbilt University could lead to new treatments The simple act of standing up can send some people’s heart racing. Now, new research may offer some important insights into this chronic and debilitating condition.
Researchers at the University of Oklahoma Health Sciences Center, the Oklahoma City Veteran’s Administration Medical Center and Vanderbilt University identified antibodies, circulating proteins in the blood that fight infections, which appear to play a role in the syndrome. The research findings are published online by the Journal of the American Heart Association.
Known in the medical field as postural tachycardia syndrome, or POTS, the hallmark of this condition is an abnormally rapid heart rate upon standing. Other chronic symptoms (lasting more than six months) may include shortness of breath, weakness upon standing as well as exercise intolerance. It affects about 500,000 people in the United States, most of them young women.
“This condition is more than a minor annoyance for most patients. It leads to significant life changes and limitations in normal life,” said study senior author David Kem, M.D., George Lynn Cross Research Professor of Medicine at the OU Health Sciences Center, a member of its Heart Rhythm Institute, who performs research and sees patients at the Oklahoma City VA Medical Center.
Jayci Robison, 19, of Cashion, Oklahoma knows all too well the life-changing impact of POTS.
“I feel my heart racing, my hands start shaking and I have to sit down,” Robison said. 2 After months of testing without answers, Robison was referred to specialists at OU Medicine, who diagnosed her with POTS.
“It’s hard for others to understand because I don’t look sick,” she said. “It’s meant a complete and total lifestyle change.”
“The cause of POTS is probably multifactorial, with different underlying causes in different patients” said co-author Satish Raj, M.D., MSCI, associate professor of Medicine and Pharmacology at Vanderbilt and Consultant at the Vanderbilt Autonomic Dysfunction Center. However, he added that the research uncovered evidence of “a history of viral-type illness” in some patients. When combined with the antibody discovery, it suggests a potential infection-induced, autoimmune- cause.
In the study, researchers evaluated blood samples from patients with POTS and also from healthy individuals. They found evidence of antibodies in blood samples from patients with POTs that bind to receptors on cells regulating vascular tone and to other receptors on cells involved in the regulation of heart rate.
“Our research found autoantibodies caused changes that altered cell function. These autoantibodies interfere with normal changes in the system that control the ability of blood vessels to become narrower and prevent the expected drop of blood pressure as the patient stands,” Kem said. The body compensates for this by increasing sympathetic nerve activity, which helps maintain blood pressure but directly speeds up the heart rate.
The OU Health Sciences Center team was led by Kem, Xichun Yu, M.D, and post-doctoral student Hongliang Li, M.D., Ph.D. The same team previously found evidence of antibodies associated with a blood pressure drop upon standing, called orthostatic hypotension. “We’re just at the beginning of a series of studies to try to understand what this means in terms of its potential for impacting the patient care in the clinic,” Raj said. “This opens up a new avenue of investigations, both to better characterize and understand the cause, and potentially to look at different treatments.”
For Robison, the research brings hope. She still plays basketball, but can only do so for about 10 minutes at a time before feeling like she will pass out. Her dreams of playing basketball in college have been derailed by POTS, but she still dreams. She now she dreams of the day when new treatments can help her reclaim her once active lifestyle.
“This condition has completely changed my life. It can hit at any time. So I bring my medications with me at all times. I try to keep the people around me educated about the condition. I stand up gradually and don’t overexert myself,” Robison said.
The research also has captured the attention of Dysautonomia International, an organization committed to helping patients with POTS. 3
"We are grateful to Dr. Raj, Dr. Kem, and the entire team of researchers who worked on this groundbreaking project," said Lauren Stiles, president of Dysautonomia International. "The POTS patient community is very excited about this research. While there is much work to be done, we are hopeful that this may lead to the development of a blood test that can be used to help diagnose POTS; and more important, new ways of treating POTS by targeting these autoantibodies. Dysautonomia International is going to do everything we can to support the researchers doing this important work."
Investigators from several institutions participated in this research team, including Luis Okamoto, M.D., research instructor in Medicine at Vanderbilt, Michael Hill, Ph.D., University of Missouri, Madeleine Cunningham, Ph.D., University of Oklahoma, Campbell Liles, Oklahoma State University, and Alexandria Benbrook, B.S., Oklahoma City University.
The research is supported by funding from a VA Medical Center Merit Review Award, an American Heart Association Postdoctoral Fellowship, the OU Health Sciences Center’s Heart Rhythm Institute, Harold Hamm Diabetes Center at the University of Oklahoma as well as by National Institutes of Health grants including HL056267, HL102387, NS065736 and TR000445.