New research explains how low levels of the electrolyte sodium in the blood can disrupt the timing of the heartbeat in patients taking widely used rhythm-control medications such as flecainide, which is commonly prescribed for atrial fibrillation and other fast or irregular heart rhythms.
The study, by Virginia Tech researchers at the Fralin Biomedical Research Institute in the journal Heart Rhythm , was conducted using guinea pig hearts and showed that blocking cardiac sodium channels with commonly prescribed medicine such as flecainide can make the heart's electrical conduction unusually sensitive to even modest reductions in blood sodium levels.
Although sodium is often associated with dietary salt, when measured in medical settings it refers to the concentration of sodium ions in the blood — a factor for nerve and muscle function. When those levels drop below a critical level, a condition known as hyponatremia, electrical signaling in the heart can become unstable, especially in patients on sodium channel blockers.
"Doctors have long known that sodium channel blockers can slow cardiac conduction, and that low sodium levels are risky," said Steven Poelzing, the study's senior author and the James and Deborah Petrine Professor with the Fralin Biomedical Research Institute at VTC. "But what wasn't clear is why the combination of the two is so problematic. This study helps explain the mechanism."
The researchers found that when sodium channels are impaired, the heart relies more heavily on backup pathways to keep electrical signals moving. One of those pathways involves electrical interactions between neighboring heart cells in very narrow spaces — a process known as ephaptic coupling.
Another pathway involves the flow of potassium ions through channels that helps reset the heart's electrical state. When sodium levels fall, these mechanisms don't compensate as they normally would, causing conduction to slow more than expected.
"If you have the right amount of sodium in your blood, electrical activity will still move through the heart at the right speed — even when sodium channels are blocked," Poelzing said. "But if you drop too low — because of vomiting, diarrhea, certain medications, or a medical condition — the drug may suddenly become detrimental."
Importantly, the study shows that interfering with either ephaptic coupling or the net outward flow of potassium ions reduces the heart's sensitivity to low sodium when sodium channels are blocked. That insight opens the door to more targeted strategies for managing conduction risks in patients who rely on sodium channel blockers.
"This doesn't mean every patient needs to worry but it is directly relevant to the clinical management of arrhythmias," said Poelzing, who is with the Fralin Biomedical Research Institute's Center for Vascular and Heart Research . "For some patients on drugs like flecainide, careful monitoring of sodium levels may be just as important as managing the arrhythmia itself."
The findings also underscore the need for physicians to be aware of hidden interactions between drug therapy and electrolyte imbalances — particularly low sodium levels — especially in older adults or hospitalized patients, who may be more prone to hyponatremia.
"The study indicates that mean sodium levels shouldn't be an afterthought — especially for those on heart rhythm medications," Poelzing said. "A quick conversation with your doctor might help prevent a more serious problem down the line."
Poelzing is also a professor of Biomedical Engineering and Mechanics in the Virginia Tech College of Engineering .
The study was led by Poelzing and William Adams, who was a student in the Translational Biology, Medicine, and Health graduate program working in Poelzing's lab when the research took place. Research Assistant Professor Hoeker was among the co-authors. The research was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health.
