Norman resident Larry Wrede didn’t know he had any problems with his heart, but when he felt his heart rate dramatically increase one evening, he knew he should see his doctor.
That visit ultimately led to his participation in an innovative research study to treat atrial fibrillation at OU Medicine.
Cardiologist Stavros Stavrakis, M.D., Ph.D., driven to improve the quality of life for patients like Wrede, was the lead author for the TREAT AF trial, which showed remarkable results for a novel way to treat the condition. The study tested a non-invasive treatment to regulate the abnormal heart rhythm of atrial fibrillation: stimulation of a nerve through a clip on the patient’s ear.
The brain controls the function of the heart by sending communications through the vagus nerve. As the largest nerve in the body, the vagus begins in the brain and travels down the neck, to the heart, and down into the stomach and intestines. But it can be stimulated on the ear. Stavrakis’ hypothesis was that an electrical stimulation on the vagus nerve could suppress atrial fibrillation. His trial was the first to study the treatment in humans.
“We found a way to non-invasively stimulate the nerve from the ear to suppress atrial fibrillation,” he said. “We’re essentially regulating the influence of the brain to the heart.”
In the study, 53 patients at OU Medicine were randomized into two groups – one receiving the actual treatment, the other receiving a sham treatment. The study was double-blinded, meaning neither the study participants nor the investigators knew which treatment was the real one. Participants receiving the real treatment were given a small device with an ear clip that they placed on the tragus – the piece of cartilage just above the ear lobe on the facial side. The device delivered a low-level electrical stimulation. Patients were asked to adjust the stimulation until they felt a mild discomfort, then decrease it a bit so it was tolerable. More than 75 percent of participants followed the daily requirements of the study, a rate similar to adherence in medication studies.
In the study, patients used the device on their own for one hour each day for six months, and they wore monitors that measured their heart rhythm. At the end of six months, the patients receiving the treatment had an 85 percent decrease in the amount of atrial fibrillation as compared to those who didn’t receive the treatment. For Stavrakis, who has worked for 10 years to bring his research to a clinical trial for humans, the news was exciting.
“We were expecting some effect from the stimulation, but this was a great effect,” he said. “The beauty of this is that it’s a low-cost, low-risk intervention.”
Notably, the stimulation had a carryover effect – atrial fibrillation was suppressed for 24 hours even though the stimulation was applied for one hour daily. That’s good news, Stavrakis said, because it means patients would not have to use the device all the time.
Even though he didn’t know whether he was using the real or sham stimulation, Wrede suspected his was the real one. His resting heart rate, which had been surging as high as 165 beats per minute, began dropping and never climbed that high again, nor as frequently. He easily worked the process into his daily routine: Every morning as he drank his coffee and read the day’s news, he did the stimulation. Participating in the study made him intrigued about the potential of stimulation as a treatment.
“It was exciting to be a part of such a cutting-edge study,” he said.
Stavrakis presented the findings of his study earlier this month to the annual meeting of the Heart Rhythm Society, the largest arrhythmia-related meeting in the world. The study is important because the global burden of atrial fibrillation is significant. The condition affects more than 33.5 million people around the world, a number that is expected to grow to 50 million in the next 20 years because of obesity and an aging population, Stavrakis said.
People with atrial fibrillation often experience shortness of breath, weakness, lightheadedness and fatigue. Stavrakis aims to improve his patients’ quality of life by reducing those symptoms and potentially decreasing the likelihood of more serious heart problems.
Because this was a small, single-center study, the next steps are to test the treatment in more patients at multiple sites across the country. Stavrakis also plans to conduct research to identify which patients would benefit the most from vagus nerve stimulation, using EKG, echocardiogram or blood draws to potentially identify a marker. In addition, he will further investigate another finding of the trial: Patients receiving the treatment also showed decreased inflammation in their blood. Because inflammation is known to play a role in many other diseases, that discovery warrants further investigation, he said.
Because he is both a physician and a researcher, Stavrakis was especially gratified by the study outcomes because his years of hard work are paying off in ways that can help his patients.
“This is one of the most exciting parts of my work because something we’ve been doing in the laboratory can now be taken to patients,” he said.