by Angela Herring

Sudden car­diac arrest is the leading cause of death in the indus­tri­al­ized world. How­ever, it’s not well under­stood and is chal­lenging to both pre­dict and effec­tively pre­vent, according to Alain Karma, Arts and Sci­ences Dis­tin­guished Pro­fessor in the Depart­ment of Physics.

“The drugs that reduce the risk for sudden car­diac death have not been suc­cessful,” said Karma, who is the director of Northeastern’s Center for Inter­dis­ci­pli­nary Research on Com­plex Sys­tems. He attrib­uted the drugs’ failure to their design, noting that they are cre­ated without con­sid­er­a­tion of the entire car­diac bio­log­ical system.

Karma wants to change that. Backed by $1.2 mil­lion in funding from the National Insti­tutes of Health, he and his col­leagues at Brown Uni­ver­sity will study how a par­tic­ular class of gene muta­tions in humans sig­nif­i­cantly increases the risk of sudden car­diac arrest by dis­turbing the heart’s elec­trical sig­naling. The work, Karma said, “will help us under­stand what kind of inter­ven­tions we can use to move the heart system from an unsafe zone to a safe zone.”

The heart, he explained, is a com­plex elec­trical cir­cuit. The key mol­e­c­ular com­po­nents of this cir­cuitry are nanoscale pro­teins embedded in the mem­brane of each car­diac cell that act as chan­nels for the flow of charged par­ti­cles such as sodium, potas­sium, and cal­cium ions. This flow gen­er­ates an elec­trical cur­rent across the cell mem­brane that is passed from cell to cell, causing each to con­tract and relax in a rhyth­mical fashion.

During a normal heart­beat the elec­trical signal prop­a­gates over the organ like a wave, Karma explained. It first causes the right and left atria to con­tract nearly simul­ta­ne­ously, fol­lowed by the right and left ven­tri­cles, respectively.

But during sudden car­diac arrest, that smooth rhythm is dis­rupted. The elec­trical wave takes the shape of a spiral, reen­tering the same area of car­diac tissue again and again. To Karma, the sig­nals look like “little elec­trical tornados.”

This spiral wave is trig­gered by an asyn­chro­nous beat at just the right moment. Some sudden car­diac arrest patients have a gene mutation—called the long QT gene—that causes cer­tain ion chan­nels to cease func­tioning prop­erly, thereby elon­gating the heartbeat.

“While most healthy people will have a few pre­ma­ture beats, they are usu­ally benign,” Karma said, “but in the set­ting of the long QT syn­drome, those pre­ma­ture beats can become much more fre­quent and cause the sudden onset of lethal car­diac arrhythmias.”

Karma’s team is using com­pu­ta­tional mod­eling to pre­dict elec­trical activity in the heart across a hier­archy of orga­ni­za­tional levels. “We model it all the way from the single ion channel to the organ scale,” he said. He hopes this will elu­ci­date how the poorly func­tioning ion chan­nels cause more of those little elec­trical tor­na­does and, by exten­sion, increased risk for sudden car­diac death.

The problem is that having the long QT syn­drome does not nec­es­sarily mean you will suffer an unex­pected heart attack. According to Karma, that one gene muta­tion causes a system-​​wide remod­eling, which depends on a com­plex array of fac­tors unique to each individual.

“Ulti­mately the therapy may have to be patient-​​specific because the remod­eling of the system can vary from patient to patient,” he explained, adding that his hope is for the com­pu­ta­tional mod­eling approach to pave the way for per­son­al­ized ther­a­pies for car­dio­vas­cular diseases.

Originally published in news@Northeastern on October 25, 2013