Medical Device Daily Associate

The results of the largest implantable cardioverter defibrillator (ICD) study to date, known as INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AVSH in ICDs), are published in the January issue of the journal Circulation, with somewhat surprising results.

Not only do the results appear to refute the notion that dual-chamber ICDs damage peoples’ hearts — as indicated in the well-known DAVID (Dual Chamber and VVI Implantable Defibrillator) study — but in fact they trend towards lower rates of mortality and heart failure hospitalization.

The INTRINSIC RV study, funded by the CRM unit of Boston Scientific (Natick, Massachusetts) (the CRM unit formerly known as Guidant), met its primary endpoint, showing that dual-chamber pacing in combination with Boston Sci’s AV Search Hysteresis (AVSH) programming — a feature designed to proactively reduce right ventricular (RV) pacing when the heart’s natural rhythm is present — performs as well as single-chamber pacing in reducing heart failure hospitalization and all-cause mortality

“The results of this landmark study are important because dual-chamber ICD programming can provide benefits to patients that single-chamber programming may not, such as improved heart function and enhanced arrhythmia detection,” Brian Olshansky, MD, told Medical Device Daily. Olshansky is a professor of medicine and a director of cardiac electrophysiology at University of Iowa Hospitals (Iowa City) and a co-lead investigator of the trial.

“Prior studies have suggested that dual-chamber devices may lead to unnecessary RV pacing, which in some patients may pose safety concerns,” he said. “This study showed that these perceived safety concerns were not present in the patient arm where dual-chamber pacing with AV Search Hysteresis was used.”

Olshansky added: “We have had only negative data on the use of dual-chamber devices based on DAVID and other studies showing that the problem appears to be related to right ventricular pacing and not the device itself. Nevertheless, CMS has recommended single-chamber shock-only devices unless there’s data demonstrating safety for dual-chamber devices or a need for dual-chamber ICDs.”

INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs) is a multi-center, randomized, prospective, non-inferiority trial that enrolled 1,530 patients with a current indication for an ICD at 108 centers in the U.S. Germany, Italy and Australia. The primary endpoint was a composite of all-cause mortality and heart-failure hospitalization. Patients in the dual-chamber pacing with AVSH group experienced 33% fewer deaths and heart-failure hospitalizations compared to single-chamber pacing.

While Olshansky said that CMS has encouraged increased use of single-chamber ICDs, he said his understanding is that the “great majority of ICDs implanted are still dual-chamber.” However, he noted one of the great flaws with dual-chamber ICDs is that these devices are being implanted with programming that’s similar to DAVID and thus apparently causing harm to patients.

He said that the programming algorithm in the dual-chamber arm of DAVID study — whose results were published in the Journal of the American Medical association in December 2002 (Medical Device Daily, Dec. 23, 2002) — was designed to employ right ventricular pacing more than 50% of the time.

“I think that’s unacceptable,” he said. He noted that data has shown that the cut-off for safe right ventricular pacing has been shown to be about 40%, and for the INTRINSIC RV study the investigators “we’re trying for less than 20% right ventricular pacing.” as their study cut-off.

The group that did the best in the study, according to Olshansky, was those patients who were pacing between 10% and 20% of the time in the right ventricle, which was twice as good as the group that was pacing between 0% and 10%, results that he termed “very surprising and very significant.”

According to Olshansky, while his group believes that the study would show that dual-chamber pacing is at least equivalent to single-chamber pacing, he said he did not anticipate the perceived trend towards better outcomes with the dual-chamber device.

During the study, a total of 32 patients (6.4%) in the dual-chamber arm of the study and 46 patients (9.5%) in the single-chamber arm of the study died or were hospitalized for heart failure during a mean follow-up of 10.4 months.

“We didn’t power the study to look at that particular issue because we didn’t expect that to happen,” he said, adding that while this mortality difference was not statistically significant, further studies may prove an advantage for dual-chamber patients with an optimized algorithm.

“I think that the goal is to try to optimize right ventricular pacing where you keep it at less than 20% and you’re also adjusting the AV interval,” he said, adding that the INTRINSIC RV study will offer other avenues to explore to optimize these pacing settings.

“I think [this study] really adds more information to think about because we don’t have data as to what that AV interval should be and the best way to deliver right ventricular pacing when it’s necessary.”