The fact that 34 % of detected FVT episodes in the shock arm of the PainFREE Rx II trial terminated during the 3.3 s (median) of capacitor charging suggested that a longer delay would further reduce unnecessary ATP [
12]. It was intuitively assumed that increased duration of tachycardia might increase syncope. However, delaying detection to a number of intervals to detect (NID) of 18 out of 24 beats (18/24) proved safe because arrhythmic syncope (8 of 1837, 0.5 %) did not increase compared with PainFREE Rx (13 of 1248, 2.0 %), which used a NID of 12/16 [
18]. The Primary Prevention Parameters Evaluation (PREPARE) study, a prospective nonrandomised cohort-controlled ICD trial which started in 2003, enrolled 700 primary prevention patients and strategically chose VT/VF detection and therapy parameters to reduce shocks and other morbidities. VT/VF was detected for rates ≥182 beats per minute (bpm) that was sustained for at least 30 out of 40 beats. ATP was programmed as first therapy for regular rhythms with rates of 182–250 bpm, and supraventricular tachycardia discriminators were used for rhythms ≤200 bpm. The control group consisted of 689 primary prevention patients from the Comparison of Empiric to Physician-Tailored Programming of Implantable Cardioverter Defibrillators (EMPIRIC) and the Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation (MIRACLE ICD) trials for whom VT/VF detection and therapy programming were not controlled. The PREPARE study demonstrated that programming a monitor zone without ICD intervention for slower VT episodes, longer arrhythmia-detection duration (i.e. NID 30/40) both in the fast VT ≥182 bpm and VF zone ≥250 bpm, and the use of supraventricular detection discrimination algorithms were associated with reductions in both appropriate and inappropriate shocks in the first year (9 vs. 17 %) and reductions in morbidity index events (0.26 events/patient-year for PREPARE study patients vs. 0.69 for control cohort patients) [
19]. In the recently completed PainFREE SST study, which started in 2009, the safety of extending VT/VF interval detection duration (18/24 vs. 30/40 intervals) is assessed. Primary prophylactic patients received a VF NID of 30/40, while secondary prophylactic patients were randomised to a VF NID of either 18/24 or 30/40 [
20]. Results from this study are expected soon. The MADIT-RIT (Reduce Inappropriate Therapy), a large-scale, randomised trial which also started in 2009, assessed the impact of high-rate cut-offs and longer delays than standard programming on inappropriate therapy in primary prevention patients receiving an ICD (dual-chamber) or CRT-D. A total of 1500 hundred patients were randomly assigned to one of three programming configurations:
conventional (VT between 170–199 bpm with a 2.5-s delay and VT/SVT discriminators turned on; VF ≥200 bpm with a 1-s delay before delivery of ATP or shock),
high rate (VT monitoring between 170–199 bpm; VF ≥200 bpm with a duration of 2.5-s) and
delayed therapy (VT-1 between 170–199 bpm, with rhythm detection on and a 60-s delay before initiation of therapy; VT-2 ≥ 200 bpm, with rhythm detection on and a 12-s delay before therapy; and VF ≥250 bpm with a 2.5-s delay before initiation of therapy). As compared with the conventional-therapy group, the high-rate and delayed-therapy groups had significantly fewer patients with a first and total occurrence of appropriate or inappropriate therapy [
21]. Findings were dominated by reductions in ATP. First occurrences of inappropriate ATP and shocks were most frequent with regular SVT and atrial fibrillation. The fact that also appropriate ATP occurred less often demonstrated that many VT episodes terminated spontaneously and did not need any ICD therapy [
21]. Finally, the ADVANCE III trial, a randomised controlled clinical trial which started in 2008, assessed whether increasing the NID is an effective strategy to further reduce appropriate and inappropriate ICD intervention in any type of ICD (single-chamber, dual-chamber, CRT-D), among patients with both primary and secondary ICD indications. ADVANCE III demonstrated that the use of a long detection setting (NID 30/40) in ICDs with the capability of delivering ATP during capacitor charge significantly reduced the rate of appropriate therapies (ATP and shocks) and inappropriate shocks compared with the standard detection setting (NID 18/24) [
13]. Mortality and syncope rates did not significantly differ between the groups. A NID of 30/40 also avoided an appropriate shock in 54 % of the sustained episodes with cycle length between 240–320 ms. These results confirmed and reinforced, in a larger population, the main results presented by the MADIT-RIT trial.