Glikson, Michael

Background The Detect Supraventricular Tachycardia (Detect SVT) trial was a randomized single blind study in subjects receiving a dual chamber implantable cardioverter defibrillator (ICD). The primary goal was to evaluate whether dual chamber enhancements result in greater discrimination between supraventricular tachycardia (SVT) and ventricular episodes when compared to ventricular-only enhancements. Purpose The purpose of this report is to describe our experiences from an analytic perspective, including overall study design, the value of blinded episode review, and the statistical analysis plan. Methods The Detect SVT study was a parallel group study, with blinded central review of all arrhythmia episodes occurring over a six-month period. The primary response was the proportion of inappropriate detections (SVT episodes that are inappropriately classified as ventricular by the device). Results A parallel group design was essential as unplanned crossovers were very differential. The blinded review of episodes was a major use of resources, with over 2300 episodes observed. This review did not materially alter the findings, however, the avoidance of any perceived bias was a major strength. The value of collecting large numbers of episodes on a single subject was found to be minimal. A Kaplan–Meier analysis of the number of SVT episodes until first inappropriate detection was found to add additional information. Limitations The recommendations reported here relate to cardiac arrhythmia trials, or other studies with very similar endpoints. These observations are based on the results of a single trial and should be confirmed in other studies. Conclusions The parallel group design was essential, as was accounting for within-subject correlation in the analysis. The blinded review process was also important, but significant resources could be saved by closing-out episode collection after a fixed number of episodes. Lessons learned from the Detect SVT trial may prove useful to others designing trials in this active research area.

Background— Delivery of inappropriate shocks caused by misdetection of supraventricular tachycardia (SVT) remains a substantial complication of implanted cardioverter/defibrillator (ICD) therapy. Whether use of optimally programmed dual-chamber ICDs lowers this risk compared with that in single-chamber ICDs is not clear. Methods and Results— Subjects with a clinical indication for ICD (n=400) at 27 participating centers received dual-chamber ICDs and were randomly assigned to strictly defined optimal single- or dual-chamber detection in a single-blind manner. Programming minimized ventricular pacing. The primary end point was the proportion of SVT episodes inappropriately detected from the time of programming until crossover or end of study. On a per-episode basis, 42% of the episodes in the single-chamber arm and 69% of the episodes in the dual-chamber arm were due to SVT. Mortality (3.5% in both groups) and early study withdrawal (14% single-chamber, 11% dual-chamber) were similar in both groups. The rate of inappropriate detection of SVT was 39.5% in the single-chamber detection arm compared with 30.9% in the dual-chamber arm. The odds of inappropriate detection were decreased by almost half with the use of the dual-chamber detection enhancements (odds ratio, 0.53; 95% confidence interval, 0.30 to 0.94; P =0.03). Conclusions— Dual-chamber ICDs, programmed to optimize detection enhancements and to minimize ventricular pacing, significantly decrease inappropriate detection.