Benefits of Long-Detection Programming Extend to Single-Chamber ICDs, Study Shows

The benefits of programming long detection intervals that have been established for dual-chamber implantable cardioverter defibrillators (ICDs) have now been shown to apply to single-chamber ICDs as well.

That’s the conclusion from a large ancillary analysis of the ADVANCE III study presented as a late-breaking clinical trial at the Heart Rhythm Society’s annual scientific sessions this week in Chicago. The study was simultaneously published online in JACC: Clinical Electrophysiology.

“We found that an optimized programming strategy using a long detection setting significantly reduced ICD therapies, shocks, hospitalizations and death among patients implanted with a single-chamber ICD,” says Cleveland Clinic cardiologist Niraj Varma, MD, PhD, the study’s senior author. “This programming strategy was strongly and consistently effective across a range of tested metrics.”

Dearth of data on single-chamber defibrillators

The investigation stemmed from growing awareness that unnecessary ICD therapies may confer adverse clinical effects.

“Strategies to limit unnecessary ICD therapies have focused on optimized programming, especially delay to delivered therapy,” Dr. Varma explains. “While this approach has won strong recommendations, the bulk of the studies supporting it have involved dual-chamber ICDs. Single-chamber ICDs have been excluded from most trials testing optimized programming strategies.”

Deeper dive into an ADVANCE III subgroup

To address that dearth of data, Dr. Varma joined with international investigators from the multicenter ADVANCE III trial that tested the effect of long detection intervals for reducing unnecessary ICD therapies. Primary results of that trial, which involved 1,902 patients implanted with single-chamber, dual-chamber or cardiac resynchronization therapy ICDs for primary or secondary prevention of cardiac death, were published in JAMA in 2013. Patients were randomized to intervention with long detection settings or standard-interval programming, and results showed that use of a long detection interval significantly reduced the rate of ventricular therapies delivered and inappropriate shocks compared with the standard detection setting.

“The primary ADVANCE III results showed that extending the duration of the monitoring delay before therapy initiation reduced ICD therapies by more than a third compared with conventional programming,” Dr. Varma observes.

The current analysis focused exclusively on the 545 subjects from ADVANCE III who received single-chamber ICDs, 267 of whom had been randomized to long detection and 278 to standard programming. The same metrics from the main trial were used, including the following outcomes of interest:

• Overall ICD therapies delivered (both antitachycardia pacing [ATP] and shocks)
• Rates of ATP and shocks individually
• Rates of appropriate therapy (i.e., delivered for monomorphic or polymorphic ventricular tachycardia and for ventricular fibrillation)
• Rates of inappropriate therapy (i.e., delivered for supraventricular episodes or nonarrhythmic events)
• Hospitalizations
• Syncope
• Death

Despite the nomenclature, even appropriate therapies were considered something to be avoided, as Dr. Varma explains: “There is consensus that unnecessary ICD therapies — whether appropriate or inappropriate — should be avoided, as evidence for their adverse effects has mounted, which include impaired quality of life, increased medical utilization and an association with higher mortality. Moreover, shocks — be they appropriate or inappropriate — may be proarrhythmic and may cause cell injury, negative inotropy and hemodynamic compromise.”

Results of the ADVANCE III single-chamber ICD analysis

Over a median follow-up of 12 months, programming long detection intervals significantly reduced therapies overall as well as ATP rates and shocks individually, as follows:

• 48 percent reduction in overall therapies compared with standard detection intervals (P = .002)
• 40 percent reduction in shocks (P = .026)
• 51 percent reduction in ATP delivery (P < .001)
• 51 percent reduction in appropriate therapies (both shocks and ATP) (P < .001)

Inappropriate therapies were infrequent overall, and while they occurred less often with long detection than with standard programming, the total number was too small for statistical comparison.

Syncope was comparably rare in the two treatment groups, but long detection was associated with advantages over standard programming in both hospitalization and mortality over 12-month follow-up, as follows:

• 27 percent versus 36 percent rate of all-cause hospitalization (P = .04), a result driven chiefly by cardiovascular hospitalization (P = .04)
• 3.0 percent versus 7.2 percent mortality (P = .047)

The findings in context

Dr. Varma notes that the finding of a 59 percent reduction in mortality with long detection programming in this analysis is noteworthy, “as these data further support the concept that reducing ICD therapies improves survival.”

He adds that these results are of particular interest since implantation of dual-chamber ICDs in patients without pacing indications is associated with an increase in complications and may be contested by payors.

“We now have the best evidence to date that optimized programming that combines a long detection setting with ATP during charge yields significant reductions in ICD therapies and improved clinical outcomes in patients with single-chamber ICDs, not just in those with double-chamber defibrillators,” he says. “The implantation of dual-chamber units simply to reduce unnecessary shock therapies because of their embedded discriminatory algorithms may not be justified.”