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 • Surgical Procedure: – Surgical pocket + Transvenous leads Hematoma • Device issues – Pocket: – Discomfort – Hematomas Pocket Infection – Infections Lead fracture – Cosmetic concerns Leads: • – Mechanical failures Infection Erosion – Infections; Extractions – Mobility restrictions Lead dislodgement – Challenge in compatibility with MRI
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 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 - <30 minute skin-to-skin procedure • Self-contained device in ventricle - No lead or surgical pocket - Inherently MRI compatible • Conventional Features -Temperature-Based Rate Response - >10-yr battery life - Hysteresis - Magnet Mode • Flexible replacement options - Catheter-based retrieval - Place additional leadless pacemakers - Revert to conventional pacing lead Proprietary and Confidential 6
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 <1 mg of dexamethasone sodium phosphate; or • Subject has a mechanical tricuspid valve prosthesis; or • Subject has a pre-existing pulmonary arterial (PA) hypertension (PA systolic pressure exceeds 40 mmHg or RV systolic pressure (RVSP) as estimated by echo exceeds 40 mmHg), or significant physiologically-impairing lung disease (have severe pulmonary disease producing frequent hospitalizations for respiratory distress or requiring continuous home oxygen); or • Subject has a pre-existing pacing or defibrillation leads; or • Subject has current implantation of either conventional or subcutaneous implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT); or • Subject has an implanted vena cava filter; or • Subject has evidence of thrombosis in one of the veins used for access during the procedure; or • Subject had recent cardiovascular or peripheral vascular surgery within 30 days of enrollment; or • Subject has an implanted leadless cardiac pacemaker.
Leadless II Clinical Trial Methodology • Pre-specified Primary Efficacy and Safety endpoints were analyzed in the first 300 patients, followed for 6 months…occurred in June 2015 (Primary Cohort) – Performance goal for the primary efficacy endpoint = 85% – Performance goal for the primary safety endpoint = 86% • All analyses were conducted with the use of exact confidence intervals for binomial proportions. • The primary efficacy end point was assessed in the – Intention-to-treat (ITT) population (All in whom implantation was attempted) – Patients with successful implant • The primary safety end point was assessed in the ITT population • Additional outcomes were assessed in all 526 patients who were enrolled as of June 2015 (the Total Cohort) • All adverse events were adjudicated by an independent CEC
Leadless II Clinical Trial Patient Flow Informed Consent Enrollment Follow Patient for No Implant 30 days, then Successful? withdraw Yes Pre-Discharge 2-Week Post Implant Visit 6-Week Post Implant Visit 3-Month Post Implant Visit 6-Month Post Implant Visit Every 6 months post implant until study completion Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Leadless II Clinical Trial Patient Demographics Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Leadless II Clinical Trial Patient Demographics Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Leadless II Clinical Trial Patient Demographics Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Leadless II Clinical Trial Procedural Characteristics Successful Implantation 96.3% 95.8% Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Leadless II Clinical Trial Primary Endpoints • Safety (Intent-to-Treat Analysis) – 280 of the 300 patients achieved endpoint (93.3%; 95% CI = 89.9 to 95.9) – This exceeded the performance goal of 86% (P<0.001) • Efficacy (Intent-to-Treat Analysis) – 270 of the 300 patients achieved endpoint (90.0%; 95% CI = 86.0 to 93.2) – This exceeded the performance goal of 85% (P = 0.007) • Efficacy (Successful implants) – 289 patients with successful device implant – 270 of the 289 patients achieved endpoint (93.4%; 95% CI = 89.9 to 96.0) – This exceeded the performance goal of 85% (P <0.001) Thus, all endpoints were achieved Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Leadless II Clinical Trial Device-Related SAEs 4 4 1.3 8 8 1.5 4 4 1.3 6 6 1.1 2 2 0.6 3 3 0.6 * 3 3 0.9 10 10 1.9 * * Includes: ischemic stroke, angina pectoris, pericarditis, acute confusion & expressive aphasia, dysarthria & lethargy post implant, contrast induced nephropathy, orthostatic hypotension with weakness, left leg weakness during implant, probable pulmonary embolism, ischemic stroke Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Freedom from SADEs Primary Cohort (n=300) Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Freedom from SADEs Total Cohort (n=526) Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Leadless II Clinical Trial Device Electrical Measurements Reddy et al, N Eng J Med doi:10.1056/NEJMoa1507192
Recommend
More recommend
