MULTIPOINT™ PACING Benefits of Cardiac Resynchronization Therapy CRT benefits heart failure patients with a wide QRS and   low LVEF Compared to RV (right ventricular) only pacing, CRT:  Improves EF, NYHA class and MWT results1  Decreases hospitalizations1,4  Reduces the risk of death2 Compared to optimal pharmacological therapy, CRT:  Reduces rates of all-cause, cardiac, and HF hospitalization3 Quadripolar CRT Systems have represented a new opportunity to improve CRT implant success and avoid common CRT complications such as high thresholds and phrenic nerve stimulation Paparella G, et al Pacing Clin Electrophysiol 2010 Cleland JG, et al N Engl J Med 2005 Anand IS, et al Circulation 2009 Tang AS, et al N Engl J Med 2010 Tomassoni G, et al Heart Rhythm 2012 SJM-MLP-0416-0052 | Item approved for U.S use only | CRT Challenge: Non-responders 43% 43% of CRT patients classified as non-responders or negativeresponders by LVESV after months (N = 302) Ypenburg, C., et al Journal of the American College of Cardiology 2009 SJM-MLP-0416-0052 | Item approved for U.S use only | MultiPoint™ LV Pacing MultiPoint™ Pacing, exclusively from St Jude Medical, delivers two pulses from the Quartet™ LV lead per pacing cycle, resulting in a more effective uniform ventricular contraction SINGLE SITE PACING MULTIPOINT™ PACING LV1 P4 M3 M2 D1 LV2 SJM-MLP-0416-0052 | Item approved for U.S use only | Goals of MultiPoint™ Pacing Pacing from TWO LV sites is designed to capture more tissue to improve:  Pattern of depolarization1 LV2  Potentially improve engagement of areas around scar tissue2 LV1  Hemodynamics3  Resynchronization4 RV MultiPoint™ Pacing allows pacing from Theis C et al Journal of Cardiovascular Electrophysiology 2009 Pappone C, et al Heart Rhythm, 2015 Rinaldi CA, et al J Interv Card Electrophysiol., 2014 Thibault B, et al J Card Fail., 2014 two LV sites through just one CRT lead SJM-MLP-0416-0052 | Item approved for U.S use only | MultiPoint™ Pacing from a Single CS Branch 10 CRT-D or 14 CRT-P VectSelect Quartet™ Vectors Ability to pace from two LV sites with independent impulses and programmable delays Vector LV1 LV2 Cathode to Anode D1  M2 D1  P4 D1  RV Coil M2  P4 M2  RV Coil M3  M2 M3  P4 M3  RV Coil P4  M2 10 P4  RV Coil 11 D1  Can 12 M2  Can 13 M3  Can 14 P4  Can SJM-MLP-0416-0052 | Item approved for U.S use only | ACUTE CLINICAL EVIDENCE International Experience MultiPoint™ Pacing acute data Electrical Mechanical Methods Hemodynamic Single Site Pacing  This study evaluated the effect of MultiPoint™ Pacing (MPP™) on the left ventricular (LV) activation pattern and hemodynamics in the same patient population  A total of 10 patients with non-ischemic cardiomyopathy underwent an acute pacing protocol that included biventricular (BiV) and up to MPP technology interventions Results  Compared with BiV, MPP technology significantly increased LV dP/dtmax (30 ±13% vs 25 ±11%, P = 0.041); reduced QRS duration (22 ±11% vs 11 ±11%, P = 0.01) and MultiPoint Pacing decreased total endocardial activation time (25 ±15% vs 10 ± 20%, P= 0.01)  MPP technology also captured significantly greater LV mass during the first 25 ms and first 50s of pacing, suggesting faster wavefront propagation throughout the LV  MPP technology improved acute hemodynamic parameters, QRS duration and activation patterns in comparison to BiV Menardi, E., et al Heart Rhythm, 2015 SJM-MLP-0416-0052 | Item approved for U.S use only | MultiPoint™ Pacing acute data Electrical Mechanical Hemodynamic Methods • Multi-center, 41 patient study • Tissue doppler imaging to assess mechanical dyssynchronny Results MultiPoint™ Pacing reduced mechanical dyssynchrony relative to conventional biventricular pacing Reduced Mean Dyssynchrony with MPP™ feature 80 70 60 50 Ts-SD (ms) • 40 30 20 10 BiV Simul p < 0.001 Best MPP feature (of tested) SJM-MLP-0416-0052 | Item approved for U.S use only | Rinaldi, C A., et al Journal of Cardiac Failure, 2013 MultiPoint™ Pacing acute data Electrical  Mechanical Hemodynamic Methods  N = 25 consecutive patients implanted with an MultiPoint™ Pacing capable CRT device  Echo evaluation performed at first follow-up Results   Reduction in dyssynchrony with MultiPoint Pacing (AS-to-P wall delay with speckle Dyssynchrony Evaluation: AS-Post wall delay (Speckle-Tracking): tracking radial strain) Improvement in EF with MultiPoint  Pacing SJM-MLP-0416-0052 | Item approved for U.S use only | 10 Osca, J., et al Heart Rhythm, 2015 MultiPoint™ Pacing Electrical acute data Mechanical Methods Hemodynamic 140 Best Best MPP™ MPP™ Config  This study evaluated the acute impact of Best CONV (Quad) MultiPoint™ Pacing (MPP™) on hemodynamic response in CRT-D patients (n = 44) RV Only 105 Results  The best MPP technology intervention significantly and ejection fraction as compared to the best conventional pacing intervention  ƒThe best MPP technology intervention improved acute diastolic function, significantly decreasing - dP/dt (min), relaxation time constant, and end- diastolic pressure as compared to the best conventional intervention  LV Pressure (mmHg) increased the rate of pressure change (dP/dt [max]), stroke work, stroke volume, 70 35 Results showed that CRT with MPP technology can significantly improve acute LV hemodynamic parameters compared to conventional pacing 150 175 200 225 LV Volume (mL) Pappone, C., et al Heart Rhythm, 2014 SJM-MLP-0416-0052 | Item approved for U.S use only | 11 250 CHRONIC CLINICAL EVIDENCE International Studies MultiPoint™ Pacing 12-month   follow-up International Methods 44 consecutive patients were randomized to receive pressure-volume (PV) loop optimized MPP™ technology or Conventional CRT (CONV) at a single center in Italy The primary endpoint was the change in end systolic volume (ESV) and ejection fraction (EF) from baseline to 12 months in the MPP technology group vs the CONV group  Response to CRT was defined as alive status and ≥ 15% decrease in ESV relative to the baseline Results  ESV and EF increase relative to baseline were significantly greater with MPP technology than with CONV (ESV: median –25% vs median –18%, P =   0.03; EF: median +15% vs median +5%, P < 0.001) At 12 months, 76% (16/21) of patients in MPP technology group were classified as CRT responders compared with 57% (12/21) in the BiV group The CRT response rate in the MPP technology group remained consistent at 76% from 3 month to 12-month follow-up PV loop-guided MPP technology resulted in greater LV reverse remodeling and increased LV function at 12 months compared with similarly optimized  Conventional CRT  Pappone, C., et al Heart Rhythm 2015 SJM-MLP-0416-0052 | Item approved for U.S use only | 13 data MPP™ Technology 12-Month Follow-Up Study Methods Improvement in the degree of response over 12-months SJM-MLP-0416-0052 | Item approved for U.S use only | 14 Pappone, C., et al Heart Rhythm 2015 Benefits of Switching from Conventional CRT to MPP™ Technology Methods  The aim of this study was to evaluate if patients receiving conventional CRT (CONV) would receive additional benefit by switching CRT programming to MPP technology (n = 8)  Patients implanted with a CRT 12 months post implant had their CRT programming switched to MPP technology after echo and NYHA class assessment and classified as responders (6/8) or non-responders (2/8) based on echo comparison to baseline  Responder was defined as ESV ≥15% relative to baseline Results  The two non-responders to CONV became responde rs with MPP technology with reduction in ESV and improvement in EF relative to the 12 month exam  The remaining patients classified as responders to CONV also experienced additional reduction in ESV and improvements in EF  The study results suggest that activating MPP technology may be a potential strategy to convert non- responders to responders or further improve response in patients already responding to conventional therapy Pappone, C., et al European Heart Journal Supplements, 2015 SJM-MLP-0416-0052 | Item approved for U.S use only | 15 MultiPoint™ Pacing Registry Methods QRS Duration and Echo Changes  N = 436 patient, 73 center Italian registry  148 patients with 6-mo follow-up  67 with MPP™ technology ‘ON’, 81 with MPP technology ‘OFF’ 40 -5 30  During implant Capture Thresholds were -10 measured (CTs) and presence of PNS Results  -15 10 P < 0.000 MultiPoint™ Pacing was programmable in 97% of patients  20 -20 At follow-up QRS was reduced and EF improved with MultiPoint Pacing % DeltaQRS Biv % DeltaQRS MPP EF baseline relative to conventional BiV MultiPoint™ Pacing Programmability CT in both CT in both Vectors CT in both CT in both Vectors Vectors < 5V < 5V and Without PNS Vectors < 3V < 3V and without PNS % MultiPoint Pacing Programmability 98 97 89 89 SJM-MLP-0416-0052 | Item approved for U.S use only | 16 Forleo, et al Europace 2015 EF Biv EF MPP Multiple quadripolar lead options to the right target vein to deliver MultiPoint™ Pacing Quartet™ 1458Q S-curve 20-30-47 mm Original SJM Advanced Quadripolar Quartet ™ 1456Q Solutions Quartet ™ 1458QL S-curve Small S-curve 20-47-60 mm 20-30-40 mm Quadra Assura™ MP C Quadra Allure MP™ RF CRT-P RT-D SJM-MLP-0416-0052 | Item approved for U.S use only | 17 Multipoint™ Pacing U.S IDE study demonstrated safety and efficacy of MultiPoint Pacing  Primary endpoint: Safety and efficacy  Response defined by composite score of Hospitalization, LVEF,  MultiPoint™ Pacing compared to the single mortality site pacing through Quadra Assura™ CRT-D Quadra Assura MP™ Quadra Allure MP™ RF SJM-MLP-0416-0052 | Item approved for U.S use only | 18 ... Multiple quadripolar lead options to the right target vein to deliver MultiPoint™ Pacing Quartet™ 1458Q S-curve 20-30-47 mm Original SJM Advanced Quadripolar Quartet ™ 1456Q Solutions Quartet... LVEF,  MultiPoint™ Pacing compared to the single mortality site pacing through Quadra Assura™ CRT-D Quadra Assura MP™ Quadra Allure MP™ RF SJM-MLP-0416-0052 | Item approved for U.S use only | 18... Quartet ™ 1456Q Solutions Quartet ™ 1458QL S-curve Small S-curve 20-47-60 mm 20-30-40 mm Quadra Assura™ MP C Quadra Allure MP™ RF CRT-P RT-D SJM-MLP-0416-0052 | Item approved for U.S use only | 17