Safety and Efficacy of a Leadless Pacemaker: Results from the LEADLESS II clinical trial Vivek Y. Reddy, MD, T. Jared Bunch, MD, Daniel J. Cantillon, MD, Rahul Doshi, MD, N.A. Mark Estes, MD, Derek V. Exner, MD, Paul Friedman, MD, Gery Tomassoni, MD, John Ip, MD, Kenneth Plunkitt, MD Icahn School of Medicine at Mount Sinai, New York, NY, Intermountain Medical Center Heart Institute, Salt Lake City, UT, Cleveland Clinic, Cleveland, OH, USC University Hospital, Los Angeles, CA, Tufts University, Boston, MA, Libin Cardiovascular Institute of Alberta, Calgary, Canada, Mayo Clinic, Rochester, MN, Central Baptist Hospital, Lexington, KY, Sparrow Research, Lansing, MI, Naples Community Hospital, Naples, FL.

• COI: St Jude Medical Inc – Grant support & Consultant • I will be discussing the use of non-FDA approved devices

Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192

2015 Pacemaker State-of-the-Art •

Standard Pacemaker Technology: – Highly mature & Overall reliable – Still includes generator, connector & lead

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Surgical Procedure: – Surgical pocket + Transvenous leads

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Device issues – Pocket: – – – –

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Hematoma

Discomfort Hematomas Infections Cosmetic concerns

Pocket Infection Lead fracture

Leads: – – – –

Mechanical failures Infections; Extractions Mobility restrictions Challenge in compatibility with MRI

Infection  Erosion Lead dislodgement

Complications of Standard Pacemakers FOLLOWPACE Study [1517 Dutch Patients] Substantial incidence of Complications – Acute: 10-15% – Chronic: 9-10%

12.4% at 2 months

c Udo et al, Heart Rhythm 9:728 –735 (2012)

Can we Avoid both Surgery & the Lead? A Fully Self-Contained Pacemaker

Spickler et al, J.Electrocardiology, 3:325 (1970)

Today’s Leadless Pacemaker System The Nanostim Device •

Percutaneous femoral vein delivery - 18F introducer /steerable catheter - 10-yr battery life - Hysteresis - Magnet Mode

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Flexible replacement options - Catheter-based retrieval - Place additional leadless pacemakers - Revert to conventional pacing lead 6

Proprietary and Confidential

Leadless Pacemaker System Implantation Procedure

Leadless Pacemaker Case Device Implanted

First-in-Man Study of Leadless Pacing LEADLESS: A 3-Center, 33-Patient Study

Reddy VY / Knops R / Neuzil P Circulation 129:1466 (2014 Ritter P, Eur Heart J doi:10.1093/eurheartj/ehv214

Leadless II Clinical Trial Overview • Prospective, multicenter, non-randomized, FDA IDE study • Objective: – To evaluate the clinical safety and efficacy of non-surgical implantation of the leadless cardiac pacemaker (LCP) system in patients who are indicated for VVI(R) pacemaker.

• Primary Endpoints: – Safety: Freedom from Serious Adverse Device Effects (SADEs) at 6 months – Efficacy: Acceptable pacing capture threshold (≤2.0 V at 0.4 msec) and a therapeutically acceptable sensing amplitude (R wave ≥5.0 mV, or a value equal to or greater than the value at implantation) through 6 mo.

• 56 Centers in the US, Canada and Australia – 100 Operators – Of which, only one had prior experience with leadless pacing

Leadless II Clinical Trial Inclusion Criteria Eligible subjects will meet all of the following: • Subject must have an indication as per guidelines: – Chronic AF with 2 or 3° AV or bifascicular BBB block, including slow ventricular rates associated with AF  55.9% – NSR with 2 or 3° AV or BBB block and a low level of physical activity or short expected lifespan  8.7% – Sinus bradycardia with infrequent pauses or unexplained syncope with EP findings  35.4% • Subject ≥18 years of age; and • Subject has life expectancy of at least one year; and • Subject is not enrolled in another clinical investigation; and • Subject is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams; and • Subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the IRB; and • Subject is not pregnant and does not plan to get pregnant during the course of the study

Leadless II Clinical Trial Exclusion Criteria Subjects will be excluded if they meet any of the following: • Subject has pacemaker syndrome, has retrograde VA conduction or suffers a drop in arterial blood pressure with the onset of ventricular pacing; or • Subject is allergic or hypersensitive to