INTRINSIC RV Trial Presented at The Heart Rhythm Society Meeting May 2006 Presented by Dr. Brian Olshansky Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs Trial

www. Clinical trial results.org INTRINSIC RV Trial: Background The goal of the trial was to evaluate dual vs. single chamber pacing among patients implanted with an internal cardioverter defibrillator (ICD) for standard indications.The goal of the trial was to evaluate dual vs. single chamber pacing among patients implanted with an internal cardioverter defibrillator (ICD) for standard indications. Presented at HRS 2006

www. Clinical trial results.org INTRINSINC RV Trial: Study Design Presented at HRS 2006  Primary Endpoint: All-cause mortality or hear failure hospitalization through one year, evaluated for non-inferiority Continued programming of DDDR AV search hysteresis (AVSH) n=502 Continued programming of DDDR AV search hysteresis (AVSH) n=502 Reprogramming to VVI-40 n=486 Reprogramming to VVI-40 n= patients, standard indications for ICD implantation, implanted with a VITALITY AVT ICD programmed to dual chamber rate adaptive pacemaker (DDDR) mode Randomized. 22% female, mean age 63 years, mean follow-up 1 year 67% of patients had coronary artery disease, 78% received beta-blockers, 64% received ACE-inhibitors and 50% received diuretics Patients with RV pacing ≤20% were randomized 988 patients, standard indications for ICD implantation, implanted with a VITALITY AVT ICD programmed to dual chamber rate adaptive pacemaker (DDDR) mode Randomized. 22% female, mean age 63 years, mean follow-up 1 year 67% of patients had coronary artery disease, 78% received beta-blockers, 64% received ACE-inhibitors and 50% received diuretics Patients with RV pacing ≤20% were randomized

www. Clinical trial results.org INTRINSIC RV Trial: Primary Endpoint INTRINSIC RV Trial: Primary Endpoint Presented at HRS 2006 The primary endpoint of death or heart failure hospitalization occurred in 6.4% of the DDDR AVSH group and 9.5% of VVI-40 group, meeting the threshold for non-inferiority.The primary endpoint of death or heart failure hospitalization occurred in 6.4% of the DDDR AVSH group and 9.5% of VVI-40 group, meeting the threshold for non-inferiority. For superiority of DDDR AVSH, p=0.072 and the risk ratio was 0.67.For superiority of DDDR AVSH, p=0.072 and the risk ratio was Primary endpoint of death or heart failure hospitalization

www. Clinical trial results.org INTRINSIC RV Trial: All – Cause Mortality INTRINSIC RV Trial: All – Cause Mortality Presented at HRS 2006 All-cause mortality also met the criteria for non-inferiority (3.6% for DDDR AVSH vs. 5.1% for VVI-40 group, p<0.001 for non- inferiority, p=0.23 for superiority).All-cause mortality also met the criteria for non-inferiority (3.6% for DDDR AVSH vs. 5.1% for VVI-40 group, p<0.001 for non- inferiority, p=0.23 for superiority). During follow-up, RV pacing in the DDDR AVSH group averaged 10%.During follow-up, RV pacing in the DDDR AVSH group averaged 10%. Primary endpoint of all-cause mortality p<0.001

www. Clinical trial results.org INTRINSIC RV Trial: Summary Among patients implanted with an ICD for standard indications, use of dual chamber DDDR AVSH pacing was non-inferior to single chamber VVI-40 pacing for death or heart failure hospitalization at one year.Among patients implanted with an ICD for standard indications, use of dual chamber DDDR AVSH pacing was non-inferior to single chamber VVI-40 pacing for death or heart failure hospitalization at one year. Results of the present trial differ from those of the DAVID trial, which showed treatment with dual-chamber pacing was associated with an increase in mortality or CHF hospitalizations by 1 year compared with ventricular backup pacing in patients with LV dysfunction and standard indications for ICD therapy but not for pacing.Results of the present trial differ from those of the DAVID trial, which showed treatment with dual-chamber pacing was associated with an increase in mortality or CHF hospitalizations by 1 year compared with ventricular backup pacing in patients with LV dysfunction and standard indications for ICD therapy but not for pacing. There are several major differences between the trials, including pacing at a lower threshold in the present trial (60 bpm vs. 70bpm in DAVID) and the patient population, which in INTRINSIC RV excluded patients with >20% pacing in the first weekThere are several major differences between the trials, including pacing at a lower threshold in the present trial (60 bpm vs. 70bpm in DAVID) and the patient population, which in INTRINSIC RV excluded patients with >20% pacing in the first week Among patients implanted with an ICD for standard indications, use of dual chamber DDDR AVSH pacing was non-inferior to single chamber VVI-40 pacing for death or heart failure hospitalization at one year.Among patients implanted with an ICD for standard indications, use of dual chamber DDDR AVSH pacing was non-inferior to single chamber VVI-40 pacing for death or heart failure hospitalization at one year. Results of the present trial differ from those of the DAVID trial, which showed treatment with dual-chamber pacing was associated with an increase in mortality or CHF hospitalizations by 1 year compared with ventricular backup pacing in patients with LV dysfunction and standard indications for ICD therapy but not for pacing.Results of the present trial differ from those of the DAVID trial, which showed treatment with dual-chamber pacing was associated with an increase in mortality or CHF hospitalizations by 1 year compared with ventricular backup pacing in patients with LV dysfunction and standard indications for ICD therapy but not for pacing. There are several major differences between the trials, including pacing at a lower threshold in the present trial (60 bpm vs. 70bpm in DAVID) and the patient population, which in INTRINSIC RV excluded patients with >20% pacing in the first weekThere are several major differences between the trials, including pacing at a lower threshold in the present trial (60 bpm vs. 70bpm in DAVID) and the patient population, which in INTRINSIC RV excluded patients with >20% pacing in the first week Presented at HRS 2006