Findings could lead to improvements in the next generation of implantable cardioverter defibrillators

For people who suffer from a rapid heartbeat condition called tachycardia, an implanted device can usually nudge the racing blood pump back into a normal rhythm by applying electrical pulses to the heart. But on rare occasions, in a twist that has baffled physicians, the anti-tachycardia pulses produce the opposite effect: they trigger an even faster and more dangerous heartbeat.

By electrically jolting cardiac cells in a lab and mapping the change in the electrical activity, biomedical engineers at Johns Hopkins may have found an answer to this mystery. Writing in the Proceedings of the National Academy of Sciences, the researchers proposed that maverick electrical waves called multiarm spirals may be causing the accelerated heartbeats. Their article appeared this week in the journal's online Early Edition and will be published in the Oct. 26 print edition.

The findings could lead to improvements in the next generation of implantable cardioverter defibrillators, devices used by tens of thousands of people with heart rhythm abnormalities. "At present, the devices can be programmed by the physician to deliver any one of many different combinations of pulse parameters, and although standard algorithms exist, the optimum algorithm is not known," said Leslie Tung, a co-author of the paper and director of the lab in which the research was conducted. Tung is an associate professor in the Department of Biomedical Engineering at Johns Hopkins.

"When the condition called ventricular tachycardia is accelerated to the point where it becomes indistinguishable from ventricular fibrillation, the patient must now receive a powerful, painful shock to restore normal rhythm, a scenario that is best avoided," said lead author Nenad Bursac, who worked on the research as a postdoctoral fellow in Tung's lab. "We are the first to show that these multiarm spiral waves can be electrically induced in sheets of cardiac cells, and we think that implanted devices could sometimes be setting off the same pattern in the heart."

Tung's lab is one of the few in the world that studies electrical activity in large-scale cardiac cell cultures. The Johns Hopkins researchers collect ventricular cells from newborn rats and remove the connective tissue. The remaining cardiac cells are placed in a nutrient solution, where they thrive and establish electrical connections with one another. The result is a roughly circular single-cell layer of cardiac cells, about 2 centimeters in diameter, situated atop a microscope cover slip.

For the experiments in their new study, Tung's team stained the cells with a voltage-sensitive dye. The researchers then used the tip of a platinum wire to administer electric pulses to the cell culture. Within milliseconds of each jolt, a wave of electrical activity moved through the culture, causing the stained cells to glow as it passed through them. An optical-fiber bundle beneath the culture captured this light show, enabling the researchers to see the shape and movement of each electrical wave as it passed through the cardiac cells.

This gave the researchers a glimpse into the type of electrical activity that takes place in the heart. In a healthy organ, these waves move smoothly through the cardiac cells, causing the muscle fibers to contract and pump blood in a coordinated manner, like soldiers marching in near lockstep. During ventricular tachycardia, however, electrical waves can often form in the shape of a single- arm spiral, throwing the cellular soldiers out of sync and into a very fast but inefficient rhythm that results in a weakened pump output. Implanted devices can deliver a series of electrical pulses to disrupt these errant waves and restore a normal heartbeat.

The Johns Hopkins researchers found that the same kind of spiral wave behavior could be reproduced in their cell cultures, making the spiral waves available for scrutiny. Just as is the case with implanted devices, when electrical pulses were administered to single-arm spirals, the waves were not always halted. Instead, they broke up into a new pattern called multiarm spirals, exhibiting complex wave dynamics and an accelerated rhythm. The researchers hypothesize that what they witnessed in the lab may mirror what happens when an implanted device inadvertently triggers an accelerated heartbeat. "The basic rules on how waves propagate and respond to electrical stimuli may best be learned in simplified models of the heart," Tung said. "With further research, it may be possible to evaluate and optimize different anti-tachycardia algorithms."

Funding for this research was provided by the Mid-Atlantic Affiliate of the American Heart Association and the National Institutes of Health.

Bursac, the lead author of the study, is now an assistant professor of biomedical engineering at Duke University. Felipe Aguel, a co-author of the study, was a postdoctoral fellow in Tung's lab when the research was conducted. He is now a staff fellow with the U.S. Food and Drug Administration.