Pacemaker tune-up works chemical wonders on damaged hearts in dogs

Study points to longer-lasting treatment benefits for congestive heart failure

Using pacemakers to electrically retune a heart damaged by long bouts of a wobbling heartbeat, where one heart muscle wall is beating sooner than the other, leads to fast improvements in the tissue levels of more than a dozen proteins key to the organ’s health, scientists at Johns Hopkins report in experiments in dogs.

The team’s findings, published online this week in the journal Circulation, are believed to be the first detailed chemical analysis of the pacemaker’s biological effects on the heart and could serve as the basis for more strategic use of combined device-plus-drug treatments for people with congestive heart failure.

“Our results really help explain how pacemakers act much like a drug, actually changing the biology of the heart, and also explain why people can feel so much better after just two to six months with the device,” says study senior study investigator and cardiologist David Kass, M.D., a professor at the Johns Hopkins University School of Medicine and its Heart Institute.

“We are learning that pacemaker therapy does profoundly more than just mechanically correct how the heart beats; in fact, it produces major chemical changes that benefit the muscle,” says lead investigator Khalid Chakir, Ph.D., a postdoctoral cardiology research fellow at Hopkins.

Each year, more than a half-million Americans are diagnosed with congestive heart failure, when the heart weakens and cannot pump enough blood to the rest of the body. One-quarter of those affected, typically men and women over age 50, will suffer from a pendulating, non-uniform contraction, requiring implantation of a pacemaker. The device electrically stimulates both sides of the heart at the same time, as part of so-called cardiac resynchronization therapy to restore unison to the heartbeat.

Current treatments with pacemakers, scientists say, can block the ill effects of an uneven heartbeat, extending people’s lives for months to years or helping them return to daily activities. But these benefits do not directly fix the cause for the delayed conduction; they merely circumvent it.

“Now that we have found that resynchronization is doing more fundamental things to the heart muscle, we should be able to better combine these devices with drugs to maximize long-term survival and outcomes,” says Kass.

Chakir says previous research has shown that a year after implantation, pacemaker resynchronization has been effective at reducing mortality in some heart failure patients by as much as 36 percent, but researchers have not until now really understood the biological effect of the devices beyond the physical mechanics of contraction.