Leadless and Subcutaneous Pacemakers and ICDs Where Are We Now and - PDF document

Leadless and Subcutaneous Pacemakers and ICDs Where Are We Now and What Is the Future? Byron K. Lee MD Professor of Medicine Samuel T. and Elizabeth Webb Reeves Endowed Chair Director of the EP Labs and Clinics University of California, San Francisco 36 th Annual Advances in Heart Disease San Francisco, CA December 2019 UCSF Cardiac Electrophysiology 1 DISCLOSURES ¡ Biotelemetry § Consulting-Moderate ¡ Biotronik § Consulting-Moderate ¡ Boston Scientific § Research Support- Significant ¡ Medtronic § Research Support- Significant ¡ Zoll Medical § Honorarium-Significant 2 1

PACING HISTORY 1952 Paul Zoll: closed chest pacing Early 1950s Furman & Robinson: intracardiac pacing 1957 Earl Bakken: wearable battery powered pacemaker 1958 Rune Elmqvist & Ake Senning: implantable pacemaker 3 The first pacemaker used at Mount Zion in 1957 built from spare parts 4 2

1958 FIRST PPM PATIENT: ARNE LARSSON 5 5 http://www.21stcentech.com/wp- content/uploads/2013/10/Evolution-of- pacemakers.jpg 6 6 3

STANDARD TRANSVENOUS PPM 7 LEAD INFECTIONS 8 4

LEAD FIBROSIS 9 LEAD EXTRACTION 10 5

RISK OF LEAD EXTRACTION Maytin et al. Heart 2011 11 COMPARISON OF LEADLESS CARDIAC PACEMAKERS (Nanostim) (Micra) * Electrogram recording capabilities not available Miller MA, Neuzil P, Dukkipati S, Reddy VY. Leadless Cardiac Pacemakers: Back to the Future – JACC 2015 12 6

N Engl J Med 2015;373:1125-1135 • 526 pts. with indications for single chamber pacing • pre-specified analysis of primary efficacy and safety endpoints at 6 months in first 300 patients. • Composite primary efficacy endpoint : therapeutically acceptable pacing threshold (≤2.0 V at 0.4 ms) and sensing amplitude (R wave ≥ 5.0 mV) • Primary safety endpoint : freedom from device related adverse events through 6 months • Primary efficacy and safety endpoints compared to historical performance goals – 85% and 86%, respectively 13 N Engl J Med 2016;374:533-541 • 725 pts. with indications for single chamber pacing • pre-specified analysis of primary efficacy and safety endpoints at 6 months in first 300 patients. • Composite primary efficacy endpoint : percentage of pts. with pacing threshold ≤2.0 V at 0.24 ms and ≤1.5 V increase since implantation • Primary safety endpoint : freedom from system-related or procedure-related major complications • Primary efficacy and safety endpoints compared to historical performance goals – 80% and 83% respectively 14 7

PRIMARY ENDPOINTS Micra IDE Clinical Trial Leadless II IDE Clinical Trial • Implantation Success : 99.2% (725 • Implantation Success : 95.8% (526 pts.) pts.) • Primary Efficacy Endpoint (300 pts.): • Primary Efficacy Endpoint (300 pts.): - 270/300 pts. ( 90% , 95% CI 86.0- - 98.3% (95% CI 96.1-99.5%, 93.2%, p=0.007) p<0.001) • Primary Safety Endpoint (300 pts.): • Primary Safety Endpoint (300 pts.): - 280/300 pts. ( 93.3% , 95% CI 89.9- - 96.0% (95% CI 93.9-97.3%, 95.9%, p<0.001) p<0.001) • Primary safety endpoint and safety • Primary safety endpoint and safety endpoints exceeded pre-specified endpoints exceeded pre-specified historical performance goals. historical performance goals. Reddy VY et al – N Engl J Med 373 :1125-1135 (2015) Reynolds D et al – N Engl J Med 2016;374:533-541 15 NANOSTIM/ST JUDE/ABBOTT LEADLESS PPM CE Mark approval in 2013 Halted in October 2016 16 8

MEDTRONIC LEADLESS PPM CE Mark approval in 2015 FDA approval in April 2016 17 Heart Rhythm July 2018 18 9

Heart Rhythm July 2018 19 Heart Rhythm July 2018 20 10

Heart Rhythm September 2018 21 Heart Rhythm September 2018 22 11

Retrieval of LCP • Short-term retrieval of LCPs have been shown to be possible – Nanostim LCP successfully retrieved in 94% (15/16 pts.) up to 1188 days post-implant (Reddy VY et al - HRS Scientific Sessions 2016) • Long-term unknown: may need to be abandoned with placement of new device – age of patient should be considered Encapsulated Nanostim device at approx. 1 year 23 HRS/ACCF EXPERT CONSENSUS STATEMENT ON PACEMAKER DEVICE AND MODE SELECTION Leadless pacemaker Estimated to be suitable for 15% of Gillis AM et al – Heart Rhythm 2012;9:1344-65 patients needing pacemakers 24 12

HISTORY OF ICD THERAPY ¡ 1966 – Conception ¡ 1969 – First experimental model ¡ 1975 -- First animal implant ¡ 1980 -- First human implant ¡ 1985 -- FDA approval 25 There was initial resistance to the idea… ¡ “ …fraught with a multitude of technical difficulties… ” ¡ “ … possible immediate and delayed deleterious effects on the myocardium…. ¡ “ …unnecessary shocks… ” ¡ “…the [rationale for] some electronic gadget manufacture [is]: ‘ It was developed because it was possible. ’” Lown B and Axelrod P. Circulation 1972; 46(4): 637 26 13

There was initial resistance to the idea… ¡ “...absence of a method for testing… Even in this age of derring-do and erosion of ethical constraints, it is unlikely that VF will be induced deliberately to ascertain performance. ” ¡ “…for whom is such a device intended?” ¡ “There is serious question whether an indication can be spelled out for the use of an implanted standby defibrillator” ¡ “If no indications can be clearly defined, why dissipate scarce health resources?” Lown B and Axelrod P. Circulation 1972; 46(4): 637 27 …AND SPIRITED RESPONSE… ¡ “Fortunately, Dr. Lown’s findings of myocardial damage due to transthoracic DC electroshock have not led to [its abandonment] by the medical profession.” ¡ “…we do not foresee difficulties in identifying populations at particularly high risk of dying from VF.” Mirowski M et al. Circulation 1973; 47: 1135 • “Are Drs. Lown and Axelrod so clairvoyant that they can see the innate impractability of someone else’s research energies…?” Moss AJ. Circulation 1973; 47: 1135 28 14

29 1980: ORIGINAL MIROWSKI AID ¡ Abdominal implant ¡ High DFT ¡ SVC thrombosis ¡ Lead fracture ¡ Insulation breakdown ¡ Retraction of coil 30 15

STANDARD TRANSVENOUS ICD 31 BOSTON SCIENTIFIC “LEADLESS” S-ICD FDA approved in Sept 2012 32 16

JACC November 2016 33 JACC November 2016 34 17

JACC November 2016 35 JACC November 2016 36 18

JACC EP December 2017 37 JACC EP December 2017 38 19

22 YO WOMAN WITH ARVC AND VT 39 22 YO WOMAN WITH ARVC AND VT 40 20

SQ-ICD PATIENT SELECTION 41 CAST TRIAL 42 21

CAST TRIAL 43 WHI TRIAL WHI Investigators et al. JAMA 2002 44 22

WHI TRIAL WHI Investigators et al. JAMA 2002 45 EMBRYONIC STEM CELL RESEARCH Gepstein et al. Discovery 2009 46 23

CONCLUSIONS ¡ Leadless pacemakers § Appear effective in the short and intermediate term § Higher risk of perforation and death § Lower risk of lead and other long term complications (so far) ¡ Subcutaneous ICDs § Appear effective long term § Less lead complications offset by more non-lead complications § More inappropriate shocks are due to oversensing rather than SVTs ¡ No RCTs showing superiority or equivalence to conventional pacemakers and ICDs 47 48 24