Bruce L. Wilkoff, M.D., F.A.C.C.; Melanie T. Gura, RN, MSN, CNS

Disclosures

April 13, 2009

1. What made you and your colleagues interested in designing and implementing the DAVID II Trial?

We designed the DAVID II Trial after the completion of the DAVID trial. The DAVID Trial compared clinical outcomes for low ejection fraction ICD patients who did not otherwise require pacing therapy randomized to either single-chamber (backup VVI pacing at 40 ppm) or dual-chamber (DDDR pacing at 70 ppm) pacing from their ICD. Patient enrollment in DAVID was stopped on Sept 30, 2002, upon recommendation of its Data Safety Monitoring Board following interim data analysis which showed that the dual-chamber debrillator arm of the study experienced a statistically significantly higher incidence of combined mortality and hospitalization for worsening heart failure than did the single-chamber arm. (JAMA. 2002 Dec 25;288(24):3115-23). With completion of the DAVID Trial, we shifted our focus to confirm the mechanism responsible for the increased mortality/hospitalization in the dual chamber ICD group. While it was clear that there was a difference between the two arms as to percentage of time in active ventricular pacing, (i.e., 60% in the dual-chamber vs. 1% in the single-chamber arm), it was not clear whether the adverse impact on combined mortality and heart failure hospitalization was the result of pacing in general or right ventricular pacing in particular. Hence, the goal of the DAVID II trial was to evaluate atrial pacing with no ventricular pacing as no worse than ventricular back-up pacing in patients with reduced left ventricular function and no clinical indication for pacing who had received a defibrillator.

2. What were the principle findings of the DAVID II Trial?

Overall, 600 patients were randomized. There was no difference in baseline characteristics between treatment arms. In the VVI-40 group, the mean age was 63 years, 15% were women, mean LV ejection fraction was 27%, and ischemic cardiomyopathy was present in 93%.

There was no difference between the groups with respect to the primary endpoint, time to death, or heart failure hospitalization (24.6% for both groups, p = 0.95). There was no difference in the primary outcome among any of the tested subgroups.

There was no difference in death (p = 0.81), heart failure hospitalization (p = 1.0), syncope (p = 0.64), atrial fibrillation (p = 0.61), or first hospitalization (p = 0.46). Quality of life was also similar between the groups.

There was a trend toward fewer inappropriate shocks in the AAI-70 treatment arm, but this did not reach statistical significance.

3. What is the clinical significance of the DAVID II Trail?

Among implantable defibrillator recipients with left ventricular dysfunction and no clinical indications for pacing, the effect of atrial pacing on event-free survival and quality of life was not substantially worse than, and was likely equivalent to, back-up only ventricular pacing. Atrial pacing may be considered a "safe alternative" when pacing is desired, but affords no clear advantage or disadvantage over a ventricular pacing mode that minimizes pacing altogether.

4. What is the best method for programming ICDs to protect against bradycardia and to ultimately optimize outcomes for our patients?

Programming strategies of ICDs should include minimizing pacing altogether, i.e., VVI-40 back-up pacing, DDI-40 back-up pacing or AAI at a rate of 70 ppm. Special algorithms designed to minimize ventricular pacing that use atrial stimulation to increase heart rate are likely to be a safe alternative in order to not adversely affect the hemodynamics or to increase the risk of heart failure or death and may reduce the incidence of atrial fibrillation.

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