PainFree SST Primary Manuscript Results James Coles, PhD Medtronic, Inc.

Background ICD shocks can be associated with: –Anxiety, 1 healthcare utilization, 2 decreased quality of life, 3 and mortality 4 ICD trials show inappropriate shock rates up to 21% 30% of all shocked episodes are inappropriate 5 1 Sears SF Jr, et al. Clin Cardiol. 1999;22: Sweeney MO, et al. Heart Rhythm. 2010;7: Schron EB, et al. Circulation. 2002;105: Poole JE, et al. NEJM. 2008;359: Powell BD, et al. Pacing Clin Electrophysiol. 2012;35: Daubert JP, et al. JACC. 2008;51: Kadish A, et al. NEJM. 2004;350: Poole JE, et al. NEJM. 2008;359: Saxon LA, et al. Circulation. 2010;122: months MADIT-II 6 29 months DEFINITE 7 45 months SCD- HeFT 8 5 years ALTITUDE 9 Incidence of Inappropriate Shocks in the ICD Population

MADIT-RIT Strategy: Moss AJ, et al. N Engl J Med. 2012;367: Study limitations: 1) No single chamber ICDs, 2) Only primary prevention pts, and 3) Limited history of AF (11%) Avoid treating slow VTs and/or delay therapy delivery for fast VTs

SmartShock Technology Oversensing/Artifact T-Wave Discrimination Lead Integrity Alert Lead Noise Discrimination Supraventricular Tachycardia Wavelet + PR Logic ® SVT Discriminators in VF Zone Non-Sustained Ventricular Tachycardia Confirmation+ 20% 65% 1 XXXX Causes of Inappropriate Shocks 1 Poole, et al. NEJM 2008;359:

Study Objectives Evaluate the inappropriate shock rate using the SmartShock ® discrimination algorithms with out-of-the-box nominal settings while allowing some discretion for physician rate programming. Primary Objectives Inappropriate shock-free rate at 1 year post-implant in Medtronic ICDs: 1. Single Chamber ICDs (n = 712) 2.Dual and Triple Chamber ICDs (n = 1,308)

Required Device Programming ZoneParameters VTAll therapies off unless history of VT Detection interval at physician discretion VFLongest Interval: 320 msec Shorter allowed if VT therapies enabled Detection (NID): 1 ⁰ Prevention: 30/40 2 ⁰ Prevention: randomized 18/24 vs. 30/40 Therapies ATP During Charging™ Rx1 = 35J shock SVT Limit: 260 msec SmartShock ® Discriminators ON: Wavelet, TWOS, Lead Noise, Confirmation+, and LIA Most parameters are out-of-box nominal values in current Medtronic ICDs

VRDRCRT-D Age (y) 62 ± 1263 ± 1368 ± 11 Secondary Prevention Indication (%) Device replacements (%) Cardiac history (%) Ischemic Cardiomyopathy Non-ischemic Cardiomyopathy History of AF, any (%) LVEF (%) 33 ± 1436 ± 1528 ± 9 NYHA class (%) I II III IV Real World Patients – Limited Exclusion

Broad Representation of Device Types

DR/CRT-D: 98.5% Inappropriate Shock Free At 1-year… 1.5% inappropriate shock incidence 2.3% inappropriate therapy incidence Only 48 of 2,019 pts had an inappropriate shock during follow-up

VR: 97.5% Inappropriate Shock Free At 1-year… 2.5% inappropriate shock incidence 3.4% inappropriate therapy incidence Only 22 of 751 pts had an inappropriate shock during follow-up

Atrial Fibrillation was the most common cause of an inappropriate shock 57% of all inappropriately shocked episodes were AF Dual/triple chamber ICDSingle chamber ICD Cause of inappropriate shock # of shocked episodes # of patients with inappropriate shock(s) # of shocked episodes (%) # of patients with inappropriat e shock(s) Atrial Fibrillation/Atrial Flutter41 (49%)26 25 (81%) 16 Other SVT (sinus tach, atrial tach, etc.) 11 (13%)83 (10%)3 Committed shock after appropriate therapy 7 (8%)70 (0%)0 Ablation procedure0 (0%)01 (3%)1 EGM noise21 (25%)62 (6%)2 T-wave oversensing4 (5%)40 (0%)0 Total84 (100%)48 31 (100%) 22

Baseline History of AF Was the Strongest Predictor of Inappropriate Shocks Patients with a history of AF had a 3-fold increased risk of an inappropriate shock Inappropriate shock rates remained low despite 30% prevalence of AF Device Type Single chamber Dual/triple chamber Age ≥ 65 years < 65 years Gender Male Female LVEF > 30% ≤ 30% QRS ≥ 120% < 120% Indication Secondary prevention Primary prevention Previous device Yes No Myocardial infarction Yes No Atrial Fibrillation Yes No Ventricular Tachycardia Yes No Anti-Arrhythmic Yes No Inappropriate shock incidence at 2 years (%)

Only 14% of Shocked Episodes Were Inappropriate At 1 year… 15% of patients received any therapy 49% of these patients received only ATP 689 Appropriately Shocked Episodes 115 Inappropriately Shocked Episodes Total Number of Shocked Episodes ATP further reduced the risk of receiving a shock for any cause

Treating Slow VTs did not increase the risk of an Inappropriate Shock Median Number of Intervals = 24 –Quartiles:16-24 Median Slow VT Zone Start = 171 bpm –Quartiles: bpm 59% of Patients had VT zone therapies enabled despite programming recommendations

PainFREE SST Conclusions SmartShock ® algorithms and evidence-based, out-of-box programmed settings in modern Medtronic ICDs result in low inappropriate shock rates Shock rates were uniformly low across a heterogeneous, real-world population representing a variety of clinical ICD device indications, treated with different types of ICDs (single, dual, and triple-chamber ICDs), and afflicted by a multitude of comorbidities including atrial fibrillation Notably, the inappropriate shock rate was unaffected by physician-tailored treatment of ventricular arrhythmias slower than 188 bpm

Indications Implantable cardioverter defibrillators (ICDs) are indicated for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias. Some ICDs are also indicated for use in patients with atrial tachyarrhythmias, or those patients who are at significant risk for developing atrial tachyarrhythmias. The RV Lead Integrity Alert (LIA) feature is intended primarily for patients who have a Medtronic ICD or CRT-D device and a Sprint Fidelis lead (Models 6949, 6948, 6931, and 6930, based on performance data. The RV LIA feature may not perform as well with a St. Jude Riata/Durata lead or a Boston Scientific Endotak lead as it does when used with a Medtronic Sprint Fidelis lead. This is because different lead designs may have different failure signatures and conditions that may or may not be detected early by the RV LIA feature. Notes for ICDs: The ICD features of the device functions the same as other approved Medtronic market-released ICDs. Due to the addition of the OptiVol diagnostic feature, the device indications are limited to the NYHA functional class II/III heart failure patients who are indicated for an ICD. The clinical value of the OptiVol fluid monitoring diagnostic feature has not been assessed in those patients who do not have fluid retention related symptoms due to heart failure. Additional notes for DR ICDs: The use of the device has not been demonstrated to decrease the morbidity related to atrial tachyarrhythmias. The effectiveness of high-frequency burst pacing (atrial 50 Hz Burst therapy) in terminating device classified atrial tachycardia (AT) was found to be 17%, and in terminating device classified atrial fibrillation (AF) was found to be 16.8%, in the VT/AT patient population studied. The effectiveness of high-frequency burst pacing (atrial 50 Hz Burst therapy) in terminating device classified atrial tachycardia (AT) was found to be 11.7%, and in terminating device classified atrial fibrillation (AF) was found to be 18.2% in the AF-only patient population studied. Contraindications ICDs are contraindicated in patients experiencing tachyarrhythmias with transient or reversible causes including, but not limited to, the following: acute myocardial infarction, drug intoxication, drowning, electric shock, electrolyte imbalance, hypoxia, or sepsis; patients who have a unipolar pacemaker implanted, patients with incessant ventricular tachycardia (VT) or ventricular fibrillation (VF), and patients whose primary disorder is chronic atrial tachyarrhythmia with no concomitant VT or VF. Brief Statement: ICDs Last Updated: Oct 2014

Warnings/Precautions Changes in a patient’s disease and/or medications may alter the efficacy of the device’s programmed parameters. Patients should avoid sources of magnetic and electromagnetic radiation to avoid possible underdetection, inappropriate sensing and/or therapy delivery, tissue damage, induction of an arrhythmia, device electrical reset or device damage. Do not place transthoracic defibrillation paddles directly over the device. Potential complications Potential complications include, but are not limited to, rejection phenomena, erosion through the skin, muscle or nerve stimulation, oversensing, failure to detect and/or terminate arrhythmia episodes, and surgical complications such as hematoma, infection, inflammation, and thrombosis. An additional complication for ICDs is the acceleration of ventricular tachycardia. See the device manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential complications/adverse events. For further information, please call Medtronic at and/or consult Medtronic’s website at Caution: Federal law (USA) restricts these devices to sale by or on the order of a physician. Brief Statement: ICDs Last Updated: Oct 2014