Researchers Identify Novel Arrhythmia Mechanism and Therapeutic Approach for the Disease

Researchers Identify Novel Arrhythmia Mechanism and Therapeutic Approach for the Disease

In a recent study published in the Journal of the American Heart Association, researchers from Ohio State University’s Dorothy M. Davis Heart and Lung Research Institute at Ohio State’s Wexner Medical Center were able to identify a novel arrhythmia mechanism and therapeutic approach to improve the disease. Specifically, the researchers identified the first coding variant of DPP6 in human ventricular fibrillation.

According to the researchers, the study findings illustrate the power of genetic approaches for the elucidation and treatment of disease when carefully integrated with clinical and basic/translational research teams.

An arrhythmia is a problem with the rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, or with an irregular rhythm. Most arrhythmias are harmless, but some can be serious or even life threatening. During an arrhythmia, the heart may not be able to pump enough blood to the body. Lack of blood flow can damage the brain, heart, and other organs.

“This particular form of arrhythmia involving both the atria and the ventricle is extremely complex. It took an integrative team of cardiologists and cardiac surgeons, pharmacists, genetic counselors, biomedical engineers, and physiologists to address this disease,” said Peter Mohler, director of Ohio State’s Davis Heart and Lung Research Institute, in a recent news release. “We are still only beginning to understand how very small differences in a person’s genetic background influence the rhythm of the heart. We hope these initial findings will help us not only address rare inherited forms of disease but also more common forms of irregular heart rhythms observed in millions of people around the world.”

The study was based on the case of a 37-year-old white man who was transferred from a community hospital after resuscitation from a witnessed cardiac arrest. He was found to be in VF and treated with CPR, defibrillation, hypothermia, and amiodarone. The presenting ECG showed partial right bundle-branch block and J-point elevation in leads V1 and V2 but was nondiagnostic for Brugada syndrome or early repolarization. Previous cardiac history was negative; family history was significant for sudden death in the patient’s mother. Cardiac magnetic resonance imaging revealed left ventricular ejection fraction of 46%.

The patient underwent genetic testing for known causes of arrhythmia, but no known genetic variants were identified. Then the researchers sequenced every protein-coding gene in the patient’s genome and found multiple variants.

The researchers identified a protein-coding variant in a gene known as DPP6. The team determined that the variant alters how heart muscle cells process electrical impulses, causing an abnormal heart rhythm.

“Finally, we could see where the problem was originating, and that allowed us to design a specific therapeutic strategy that normally would not have been considered,” said Cynthia Carnes, a professor in Ohio State’s College of Pharmacy and arrhythmia researcher at the Davis Heart and Lung Research Institute. “While we are still working to understand the complete picture of this disease, this therapy has significantly reduced the patient’s irregular heart rhythms for nearly two years.”

“We are excited about these preliminary findings, and we’re now focusing on how other genetic or environmental factors may contribute to the disease,” said Amy Sturm, certified genetic counselor at Ohio State’s Wexner Medical Center and co-first author on the study. “It’s important to identify others across the globe with this form of arrhythmia to better understand the disease progression, with the ultimate goal of identifying and treating those at risk before arrhythmia occurs.”

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