Dr. Dejan Mijic Leadless Cardiac Pacemakers Department for Cardiology and Angiology Klinikum Luedenscheid Germany 13. November 2014 Klinikum Luedenscheid Germany

3 Agenda  Common pacing challenges  Leadless Pacemaker  Clinical and preclinical data  First-in-Man Study: Safety and efficacy  Retrieval safety data Dr. Dejan Mijic

4 Background Dr. Dejan Mijic

ComplicationOccurrenceImplications Lead dislodgement2.2% to 3.7% 1 Increase pacing threshold, failure to capture or sense Pneumothorax1.6% to 2.6% 1,2,3,4,5 Respiratory distress and prolonged hospitalization (80% require chest tube) Lead perforationLess than 1% 1,2 Cardiac tamponade, death Venous thrombosis1%-3% 2,3,4,5 Mostly asymptomatic Chronic Lead failure2%-4% of pts at 5 years 2,3,4,5 Failure to pace or sense Need intervention Hematoma requiring surgical evacuation <0.5% 2 Prolonged hospitalization/reoperation Increased rate of infection Skin erosion (generator change) % 2,6 Entire system (device and leads) needs to be removed Infection< 1% for single-chamber 1% - 2% for dual-chamber devices 7,8 Removal of the complete system to treat effectively 5 Complications Associated with Pacemakers 1.Pakarinen et al., Europace 2010;12(1): Gul et al., Borek et al., J Interv Card Electrophysiol 2008;23(1): Klutstein et al., Pacing Clin Electrophysiol 2009;32(Suppl 1):S Tischer et al., Europace Kiviniemi et al., Pacing Clin Electrophysiol May; 22(5): Aggarwal et al., Br Heart J 1995; 73: , 8.Chauan et al., Pacing Clin Electrophysiol 1994; 17: Dr. Dejan Mijic

J Thorac Cardiovasc Surg 1996: 111: Am J Cardiology 2000: 85: Cost index: 6 Incidence of Lead and Pocket Complications Over people are implanted annually worldwide > Nearly experience post-implant related problems Over 4.4 million people worldwide currently have a pacemaker > chronic lead related problems annually Dr. Dejan Mijic

7 Addressing the Clinical and Economic Burden of Traditional Pacing Systems There is a need for a novel system that provides reliable pacing and sensing but addresses the challenges of current pacing systems by  Minimizing the risks of infection, pneumothorax, dislodgement, long-term infection, and other complications associated with a lead and/or device pocket Ideally this system should also offer features aimed at  Improving patient comfort  Offering MRI compatibility*  Allowing for safe and easy device retrieval A cardiac pacing system that eliminates the need for transvenous leads and a subcutaneous pulse generator may have several advantages over conventional pacing systems Dr. Dejan Mijic

8 Proposed Implantation System Spickler et al., J. Electrocardiology, 3: 325 (1970) Dr. Dejan Mijic

9 Leadless Cardiac Pacemaker Nanostim™ (St. Jude Medical) Electrode with steroid elution (E); paces, senses and communicates Helix (D) provides primary fixation > Tines (angled nylon sutures) add secondary fixation Compact header (C) with no connector Battery (B) > Lower resistance due to lack of lead > Low-power conductive communication Docking feature (A) for delivery, repositioning and retrieval Tethered test mode for perioperative evaluation Dr. Dejan Mijic

10 Leadless Cardiac Pacemaker Percutaneous femoral vein delivery - 18F introducer / steerable catheter - Single operator design with flush ports - Integrated protective sleeve - Tethered feature Self-contained device in right ventricle - No lead or surgical pocket - VVIR w/ Hysteresis - Inherently MRI compatible Replacement options - Catheter based retrieval - Deliver additional leadless pacemakers - Revert to conventional pacing lead Dr. Dejan Mijic

11 Retrieval Catheter System 18F device, Single Operator Either single loop or triple loop snare Deflectable > 270° with twist lock Snare control handle * Snare Closure Knob with lock * Grab, dock / re-dock and unscrew the LCP Dr. Dejan Mijic

13 First-in-man LEADLESS study Objective: Evaluate the safety and performance of the leadless pacemaker Prospective, non-randomized, multicenter study conducted at 3 European centers A total of 33 patients were enrolled – Mean age of 75 years (53-91 years); 64% male – 60% chronic AF and high degree AV block – 28% infrequent pauses or unexplained syncope – 24% sinus rhythm with low activity or short lifespan Procedure Femoral venous access LP assessment & programming Post-Procedure 2 View X-ray of pacemaker LP assessment & programming 2-week follow-up Six-minute walk test LP assessment & programming 6-week follow-up Six-minute walk test LP assessment & programming 3-month follow- up LP assessment & programming Reddy V et al., Heart Rhythm Society 2013, Denver, CO. Dr. Dejan Mijic

14 LEADLESS Study: Delivery procedure Reddy V et al., Heart Rhythm Society 2013, Denver, CO. Successful delivery in 32/33 patients (97%)* Procedure Times –Introducer in/out: 28 minute (range 11 – 74 min) –Catheter in/out: 16 minute (range 3 – 57 min) Time from procedure to hospital discharge: Mean 1 day (Range 1 – 4) Number of times LP was repositioned: Mean 0.5 (Range 0 – 3) Times LP repositioned Number of patientsPercent of patients 02370% 1412% % *One patent had a groin hematoma that required no treatment. In another patient, there was a cardiac perforation and tamponade which required an uncomplicated surgical repair. However, during the patient’s convalescence, at 5 days post-procedure, the patient had a large right-sided stroke and later expired. Dr. Dejan Mijic

15 LEADLESS Study LCP performance is reliable and predictable Reddy V et al., Heart Rhythm Society 2013, Denver, CO. Dr. Dejan Mijic

16 Preclinical Results Retrieval Safety Sperzel et al., Europace 2013; 15(Suppl 2):859. Preclinical study in 10 sheep – Implant duration >5 months (range days) – 100% successful LP retrieval – Average time from retrieval catheter insertion to removal of LP 2 minutes 35 seconds (range 1-4 minutes) – Average delivery time for re-implantation from delivery catheter 2 minutes 42 seconds (range: 2-3 minutes) with 100% success (n=5) – Mild endocardial fibrosis – No embolization – No dislodgement – No perforations Dr. Dejan Mijic

17 Micra™ Trancatheter Pacing System (Medtronic) o 25.9 mm, < 1cc miniaturized VVIR pacemaker o World’s smallest, minimally invasive pacing system o 10 year longevity o Percutaneous access to RV apex via femoral vein o Active fixation via 4 self-expanding “tines” Dr. Dejan Mijic

18 Micra™ Clinical Trial (Medtronic) Single-arm, multi-center global clinical trial Up to 780 patients At ~50 centers Primary Outcomes at 6 months: –Safety: Major complication-free rate –Efficacy: Low and stable pacing capture thresholds Initial results Expected: –First 60 patients followed to 3 months –Expected in 2 nd half of 2014 Dr. Dejan Mijic

19 Take Home messages... The Future of Pacing is leadless! Leadless right ventricular cardiac pacing is feasible Relatively small feasibility studies raise the possibility of elimination what has been the weak link in pacemakers: The lead Retrieval is a necessary capability for leadless pacemakers: the feasibility, efficacy and safety has been shown in sheeps Further studies are necessary with longer follow up and more subjects to support broad utilization of this technique In development: Atrial LCP -> multi-chamber cardiac pacing Dr. Dejan Mijic