Cardiac Resynchronization Therapy (CRT) Is an Effective Treatment for Heart Failure and Indications Are Expanding Multiple trials have shown the clinical value of CRT: decreased mortality, improved quality of life, and reduced hospitalizations.1-5 Today, more patients than ever are available to receive a CRT device and benefit from this therapy. 郭航远 绍兴市人民医院 1 Cleland JG, et al. N Engl J Med. 2005;352:1539-1549. 2 Cleland JG, et al. Eur Heart J. 2006;27:1928-1932. 3 Bristow MR, et al. J Card Fail. 2000;6:276-285. 4 Abraham WT, et al. N Engl J Med. 2002;346:1845-1853. 5 Young JB, et al. JAMA. 2003;289:2685-2694.

CRT Is Highly Beneficial1-8 CRT is an effective treatment for heart failure patients with: • systolic dysfunction • ventricular electrical conduction delays Mortality HF or CV Hospitalizations Cardiac Function/ Structure QoL or NYHA CARE-HF1,2 + NA COMPANION3 MIRACLE4 MIRACLE ICD5 REVERSE6 +* = RAFT7 MADIT CRT8 Objective: Reinforce large scale trials have shown CRT is beneficial for heart failure patients. Questions: What are the biggest challenges of HF hospitalizations for your clinic/hospital/reimbursement/patients? What are your biggest challenges in managing your HF patients? What is the biggest challenge in improving your patients’ QOL? Say: Large trials have shown that CRT is an effective treatment for HF patients. Studies of CRT began almost 15 years ago. Over that time, we have seen that CRT reduces morbidity, mortality and HF hospitalizations in Class III and ambulatory Class IV patients. More recent trials confirmed that benefits seen in the more symptomatic population could extend to less symptomatic heart failure patients (RAFT, REVERSE, MADIT CRT). NA = Not powered, not collected, or not blinded for specific end point. * Post-hoc analysis. 1 Cleland J, et al. N Engl J Med. 2005;352:1539-1549. 2 Cleland J, et al. Eur Heart J. 2006;27:1928-1932. 3 Bristow M, et al. J Card Fail. 2000;6:276-285. 4 Abraham W, et al. N Engl J Med. 2002;346:1845-1853. 5 Young J, et al. JAMA. 2003;289:2685-2694. 6 Linde C, et al. JACC. 2008;52:1834-1843. 7 Tang A, et al. N Engl J Med. 2010;363:2385-2395. 8 Moss A, et al. N Engl J Med. 2009;361:1329-1338.

Number of Patients Receiving CRT May Increase in Coming Years Due to: • Expansion of indications for CRT-D devices to NYHA Class II1-3* • Under-penetration of current NYHA Class III/IV indications4,5 * Indications for CRT-D devices include "Left bundle branch block (LBBB) with a QRS duration ≥ 130 ms, left ventricular ejection fraction ≤ 30%, and NYHA Functional Class II" 1 Tracy CM, et al. Circulation. 2012;126:1784-1800. 2 Tang AS, et al. N Engl J Med. 2010;363:2385-2395. 3 Linde C, et al. J Am Coll Cardiol. 2008;52:1834-1843. 4 Epstein AE, et al. Circulation. 2008;117:e350-e408. 5 Fonarow GC, et al. Circ Heart Fail. 2008;1:98-106.

Current Challenges with CRT Unpredictable CRT Implant Times CRT Challenges Suboptimal CRT Response

Clinical & Economic Need: CRT Implants Are Complex and Time-Consuming Initial CRT Device Implants (N=870)1 1 PPDA Q3FY12/Q4FY12/Q1FY13/Q2FY13 - (Waves 1-4): Economic Considerations for CRT Implants

Clinical & Economic Need: Placing the LV Lead Is Time-Consuming 1 PPDA Q4FY12/Q1FY13 - (Waves 2 and 3): Economic Considerations for CRT Implants. 2 Bax JJ, et al. J Am Coll Cardiol. 2005;46:2168-2182.

Current Challenges with CRT Unpredictable CRT Implant Times CRT Challenges Suboptimal CRT Response

% Improved Clinical Composite Score Up to 1/3 of Patients Do Not Experience the Full Benefits of CRT 67% 58% MIRACLE1 MIRACLE MIRACLE II InSync III PROSPECT5 FREEDOM6 ICD2 ICD3 Marquis4™* 100% 69% 52% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% % Improved Clinical Composite Score * AV optimized only 1 Abraham WT, et al. N Engl J Med. 2002;346:1845-1853. 2 Young JB, et al. JAMA. 2003;289:2685-2694. 3 Abraham WT, et al. Circulation 2004;110:2864-2868. 4 Chung ES, et al. Circulation. 2008;117:2608-2616. 5 van Gelder BM, et al. J Cardiovasc Electrophysiol. 2008;19:939-944. 6 Abraham WT, et al. Late-Breaking Clinical Trials, HRS 2010. Denver, Colorado.

There Are Many Drivers for CRT Non-Response1 201303559 EN There Are Many Drivers for CRT Non-Response1 Potential Reasons for Suboptimal CRT Response 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Percentage of Nonresponder Patients with These Findings Suboptimal AV Timing Arrhythmia Anemia Suboptimal LV Lead Position < 90% Biventricular Pacing Suboptimal Medical Therapy Persistent Mechanical Dyssynchrony Underlying Narrow QRS Compliance Issues Primary RV Dysfunction Mullens W, et al. JACC. 2009;53:765-773. Achieving maximum CRT response requires a multi-disciplinary approach 1 Mullens W, et al. J Am Coll Cardiol. 2009;53:765-773.

Economic Impact Lab Capacity Length of Stay1 Staff Overtime Unpredictable CRT Implant Times CRT Challenges Suboptimal CRT Response Staff Overtime Supply Usage In today’s healthcare environment, hospitals and administrators are increasingly being measured on quality performance, improved outcomes, and cost metrics.1 Larger time blocks may be scheduled for CRT implants to account for variability Last scheduled procedure of the may need to be moved to the next day or the next available time- one day in the hospital for a hf patient costs $800-$1550 per day There is an implanter in South Hampton, United Kingdom- Professor John Morgan- one of the leading implanters in the world. I asked him about this very issue- about how many device cases get bumped and rescheduled to the next day or later? He answered, “At least 50% of our cases scheduled at the end of the day are ultimately moved.” Staff may work overtime to complete all scheduled procedures Multiple lead and delivery tools may be used if initial implant is unsuccessful On average, a HF admission costs a hospital more than $8,000 HF Hospital Admissions1 1 Cost information from 2010 Premier hospital database analyzing 108,982 Inpatient Heart Failure Admissions (Abstract Submission to ISPOR and AHA QCOE, to be presented in July 2013).

Real-Time Navigation for CRT Implants The CardioGuide™ Implant System Provides a Solution The CardioGuide Implant System – the first real-time navigation system for CRT implants – uses computer technologies to guide implanters in optimal LV lead placement. The system generates 3D images of coronary vessels to help clinicians: • Find appropriate LV lead locations • Identify proper lead delivery tools • Confirm final lead position 11

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CardioGuide 3D System: Optimize LV Lead Implant Shoot 2+ venograms Trace veins of interest on both venograms Obtain 3D model automatically  Understand and Examine Vein Anatomy

CardioGuide 3D System: Optimize LV Lead Implant Select preferred target site and choose LV lead Navigate real-time in fluoro Obtain anatomical information about target & match best lead Detect where lead is & how far from target

CardioGuide M-Map System: Drive for Full Benefit of CRT Obtain contraction timing maps along veins Select most appropriate delayed site and choose LV lead Identify latest site(s) of mechanical activation

Drive for Full Benefit of CRT Helping clinicians choose the proper lead location and providing confirmation of final lead position may impact CRT procedure efficiency and the economic welfare of the hospital.1-4 1 Giannola G, et al. Europace. 2011;13:244-250. 2 Khan FZ, et al. Europace. 2011;13:845-852. 3 Khan FZ, et al. J Am Coll Cardiol. 2012;59:1509-1518. 4 Prinzen FW, et al. J Cardiovasc Transl Res. 2012;5:188-195.

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