New England Journal of Medicine Study Shows Dramatically Reducing Pacing to Right Ventricle Cuts Risk of Persistent Atrial Fibrillation in Pacemaker Patients

Treatment with Medtronic’s Dual Chamber Minimal Ventricular Pacing Technologies Led to 40 Percent Reduction in Relative Risk Compared with Conventional Dual Chamber Pacing

Medtronic, Inc. (NYSE: MDT) today announced that reducing right ventricular pacing to less than 10 percent in patients with dual chamber pacemakers reduced the relative risk of developing persistent atrial fibrillation (AF) by 40 percent compared with conventional dual chamber pacing in a trial of more than 1,000 patients with sinus node disease. The trial, called SAVE PACe (The Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction) was funded by Medtronic and is published in this week’s The New England Journal of Medicine.

The trial’s objective was to demonstrate that dramatically reducing unnecessary right ventricular pacing can reduce the development of persistent atrial fibrillation. AF, an electrical malfunction of the upper chambers of the heart (atria) that can lead to irregular heartbeats, is the most common side effect of pacemakers, and can cause stroke or death. Most Medtronic pacemakers available today, including the devices used in the trial, boast proprietary features called Managed Ventricular Pacing (MVP™) or Search AV+™ that allow doctors to dramatically reduce unnecessary pacing to the right ventricle (lower chamber), which past studies have shown may lower the risk of developing AF and heart failure. SAVE PACe, the first prospective, randomized controlled study looking at the effect of reduced right ventricular pacing on AF, shows the benefits of Medtronic’s technology in preventing the development of persistent AF.

“This is the first study to demonstrate a clear superiority of newer forms of dual chamber pacing for sinus node disease versus older pacemaker technology,” said Dr. Michael O. Sweeney, of Brigham and Women’s Hospital in Boston, who served as the trial’s lead investigator. “Whereas previously some skepticism existed because of inherent uncertainties in retrospective analyses, I think the SAVE PACe trial will end that debate entirely, and hopefully, will redirect evidence-based guidelines for treatment of patients with sinus node disease toward aggressive reduction in potentially harmful right ventricular pacing.”

After an average of 1.7 years in the study, 68 patients who received conventional dual chamber pacing developed persistent AF (12.7 percent), compared with 42 patients (7.9 percent) who received “dual chamber minimal ventricular pacing,” which uses algorithms designed to minimize unnecessary pacing to the right ventricle of the heart. The study showed that patients in the treatment arm saw unnecessary right ventricular pacing reduced by greater than 90 percent. Mortality was similar in the two patient groups, but heart failure hospitalizations were greater than 50 percent lower for the patients who did not develop persistent AF (3.2 percent vs. 7.3 percent for those who did develop persistent AF). The trial was stopped early after an interim analysis revealed that patients not utilizing the algorithms designed to reduce right ventricular pacing showed a 1.8 times greater risk of developing persistent AF than those using the algorithms. This difference was highly statistically significant.

Unlike single chamber pacemakers, which control only the heart’s right ventricle, dual chamber pacemakers deliver small electrical pacing pulses to both the right ventricle and the right atrium.

Scientists hypothesized that right ventricular apical stimulation during dual chamber pacing has adverse effects on left ventricular pump function, and retrospective analyses support this hypothesis by linking the frequency of right ventricular paced beats to increased risks of atrial fibrillation and heart failure in patients with sinus node disease.

Nearly all of Medtronic’s currently manufactured dual chamber pacemakers feature either MVP or Search AV+ modes that provide the benefits of dual chamber pacing while limiting stimulation to the right ventricle to only when necessary. The MVP pacing mode, in the Medtronic Adapta™ and EnRhythm® pacing systems, is designed to promote natural heart activity by dramatically reducing unnecessary right ventricular pacing, which is accomplished by automatically switching between single- and dual-chamber pacing based on specific patient needs. With the MVP mode, automatic switching between dual chamber pacing and single chamber atrial pacing can reduce the amount of ventricular pacing to less than 5 percent, compared to 50 percent or more with typical dual-chamber pacing.

Search AV+, available in Medtronic Versa™, Sensia™ and EnPulse® pacing systems, senses the patient’s natural heartbeats before delivering pacing therapy, which may reduce unnecessary electrical impulses in the ventricle and allow the heart to beat on its own as often as possible.

“The results of the SAVE PACe trial highlight our ongoing commitment to innovation in the pacemaker market,” said Pat Mackin, senior vice president and president of the Cardiac Rhythm Disease Management business at Medtronic. “We invested in the research and development of the proprietary MVP mode, and invested in the prospective, randomized SAVE PACe trial that provides the clinical evidence that Medtronic’s new pacing strategies have a dramatic impact on patients by first reducing unnecessary pacing, which leads to a reduction in the development of persistent AF, and in turn has been proven to reduce heart failure hospitalizations. We are excited by the results of this study, which clinically prove that Medtronic’s newer pacing products have a unique beneficial impact on the lives of patients with heart disease.”