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 stimulation5 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  Potentially improve engagement of areas around scar tissue2  Hemodynamics3  Resynchronization4 LV2 LV1 RV 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 MultiPoint™ Pacing allows pacing from 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 Ability to pace from two LV sites with independent impulses and programmable delays 10 CRT-D or 14 CRT-P VectSelect Quartet™ Vectors 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  This study evaluated the effect of MultiPoint™ Pacing (MPP™) on the left ventricular (LV) activation pattern and hemodynamics in the same patient population Hemodynamic Single Site Pacing  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 decreased total endocardial activation time (25 ±15% vs 10 ± 20%, P= 0.01) MultiPoint Pacing  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 Ts-SD (ms) • 80 70 60 50 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 tracking radial strain)  Improvement in EF with MultiPoint Pacing Dyssynchrony Evaluation: AS-Post wall delay (Speckle-Tracking): SJM-MLP-0416-0052 | Item approved for U.S use only | 10 Osca, J., et al Heart Rhythm, 2015 MultiPoint™ Pacing acute data Electrical Mechanical Hemodynamic 140 Methods Best MPP™ Config  This study evaluated the acute impact of MultiPoint™ Pacing (MPP™) on hemodynamic response in CRT-D patients (n = 44)  The best MPP technology intervention significantly increased the rate of pressure change (dP/dt [max]), stroke work, stroke volume, and ejection fraction as compared to the best conventional pacing intervention  ƒ The best MPP technology intervention improved acute diastolic function, significantly decreasing dP/dt (min), relaxation time constant, and enddiastolic pressure as compared to the best conventional intervention  Results showed that CRT with MPP technology can significantly improve acute LV hemodynamic parameters compared to conventional pacing LV Pressure (mmHg) Results Best CONV (Quad) RV Only 105 70 35 150 175 200 225 250 LV Volume (mL) Pappone, C., et al Heart Rhythm, 2014 SJM-MLP-0416-0052 | Item approved for U.S use only | 11 CHRONIC CLINICAL EVIDENCE International Studies MultiPoint™ Pacing 12-month follow-up International data  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 MPP™ Technology 12-Month Follow-Up Study Methods Improvement in the degree of response over 12-months Pappone, C., et al Heart Rhythm 2015 SJM-MLP-0416-0052 | Item approved for U.S use only | 14 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 responders 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 nonresponders 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 40 -5 30  During implant Capture Thresholds were measured (CTs) and presence of PNS -10 20 Results -15 10   148 patients with 6-mo follow-up 67 with MPP™ technology ‘ON’, 81 with MPP technology ‘OFF’  MultiPoint™ Pacing was programmable in 97% of patients P < 0.000 -20  At follow-up QRS was reduced and EF improved with MultiPoint Pacing relative to conventional BiV % DeltaQRS Biv % DeltaQRS MPP EF baseline EF Biv EF MPP MultiPoint™ Pacing Programmability % MultiPoint Pacing Programmability CT in both Vectors < 5V CT in both Vectors < 5V and Without PNS CT in both Vectors < 3V CT in both Vectors < 3V and without PNS 98 97 89 89 SJM-MLP-0416-0052 | Item approved for U.S use only | 16 Forleo, et al Europace 2015 Multiple quadripolar lead options to the right target vein to deliver MultiPoint™ Pacing Quartet™ 1458Q S-curve 20-30-47 mm Original Quartet ™ 1456Q Small S-curve SJM Advanced Quadripolar Solutions Quartet ™ 1458QL S-curve 20-47-60 mm 20-30-40 mm Quadra Assura™ MP CRT-D Quadra Allure MP™ RF CRT-P 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, mortality  MultiPoint™ Pacing compared to the single 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 Quartet ™ 1456Q Small S-curve SJM Advanced Quadripolar Solutions Quartet... LVEF, mortality  MultiPoint™ Pacing compared to the single 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... SJM Advanced Quadripolar Solutions Quartet ™ 1458QL S-curve 20-47-60 mm 20-30-40 mm Quadra Assura™ MP CRT-D Quadra Allure MP™ RF CRT-P SJM-MLP-0416-0052 | Item approved for U.S use only | 17 Multipoint™